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Cui Z, He J, Li A, Wang J, Yang Y, Wang K, Liu Z, Ouyang Q, Su Z, Hu P, Xiao G. Novel insights into non-coding RNAs and their role in hydrocephalus. Neural Regen Res 2026; 21:636-647. [PMID: 39688559 DOI: 10.4103/nrr.nrr-d-24-00963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 11/16/2024] [Indexed: 12/18/2024] Open
Abstract
A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation. This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus, one of the most common neurological conditions worldwide. In this review, we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition. Then, we outline the definition, classification, and biological role of non-coding RNAs. Subsequently, we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail. Specifically, we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus, including glymphatic pathways, neuroinflammatory processes, and neurological dysplasia, on the basis of the existing evidence. Lastly, we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.
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Affiliation(s)
- Zhiyue Cui
- Department of Diagnostic Radiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan Province, China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Jian He
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - An Li
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Junqiang Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Yijian Yang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Kaiyue Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Zhikun Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Qian Ouyang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Department of Neurosurgery, Zhuzhou Hospital, Central South University Xiangya School of Medicine, Zhuzhou, Hunan Province, China
| | - Zhangjie Su
- Department of Neurosurgery, Addenbrooke 's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, UK
| | - Pingsheng Hu
- Department of Diagnostic Radiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan Province, China
| | - Gelei Xiao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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Wang L, Gu Y, Shen C. Transcriptome analysis and lncRNA expression profile in brain tissues of neonatal hypoxic-ischemic brain damage rat model. Gene 2025; 952:149363. [PMID: 40064305 DOI: 10.1016/j.gene.2025.149363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 03/21/2025]
Abstract
BACKGROUND AND OBJECTIVE Neonatal hypoxic-ischemic encephalopathy (HIE) remains a critical challenge in perinatal medicine. This study aimed to elucidate the transcriptomic landscape, focusing on long non-coding RNAs (lncRNAs) expression patterns in the brain tissues of a neonatal rat model of HIE. METHODOLOGY We employed a modified Rice-Vannucci model to induce HIE in postnatal day 4 (P4) rats. The experimental groups were subjected to either 5 or 7 min of hypoxia (0 % O2, 100 % N2), while control animals were exposed to normoxic conditions. RESULTS RNA sequencing revealed a complex transcriptomic landscape in HIE brains, with approximately 80 million differentially expressed lncRNAs compared to controls. ELISA results demonstrated a significant upregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and a concomitant decrease in anti-inflammatory IL-10 levels in brain tissue of HIE rats. qRT-PCR analysis revealed aberrant expression of several miRNAs. Biochemical assays indicated a marked reduction in superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) content in HIE brain tissues. CONCLUSIONS This study highlights the potential regulatory roles of lncRNAs in HIE brains. The intricate interplay between lncRNAs, miRNAs, and mRNAs and alterations in inflammatory and oxidative stress markers suggests a complex regulatory network governing HIE pathogenesis.
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Affiliation(s)
- Limin Wang
- Department of Pediatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China
| | - Yanni Gu
- Department of Fever Emergency, Shanghai TCM-Integrated Hospital, Shanghai 200082, China
| | - Chaobin Shen
- Department of Pediatrics, Shanghai TCM-Integrated Hospital, Shanghai 200082, China.
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Liang M, Xie J, Huang Y, Wang Q, Huang R, Liao Y, Deng Y, Yang C, Zheng Z. Identification of long non-coding RNAs and their multiple regulation mechanism in shell deposition of pearl oyster. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART D, GENOMICS & PROTEOMICS 2025; 54:101415. [PMID: 39826290 DOI: 10.1016/j.cbd.2025.101415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 01/08/2025] [Accepted: 01/08/2025] [Indexed: 01/22/2025]
Abstract
Biomineralization to fabricate diverse morphology shell is typical character of bivalve species and ectopic calcification to form is the production of defense. Long non-coding RNAs (LncRNAs) plays critical roles in multiple cellular biological processes in invertebrate and vertebrate. However, LncRNAs remain poorly understood about expression and regulation roles in bivalve biomineralization studies. In this research, we systematically identified lncRNAs that functioned in differentiated mantle regions for fabricating two phenotypes of CaCO3 crystal shell, along with pearl sac depositing pearls for ectopic calcification by CaCO3. A total of 48,555 non-coding transcripts were obtained. 229 differentially expressed lncRNAs in mantle tissue as well as 401 differentially expressed lncRNAs in the comparison of mantle center to pearl sac were identified. By cis- and trans-regulation ways, these DELs could be involved in provisioning and metabolism such as chitin, glycosaminoglycan, ECM/shell matrix protein, Ca2+ and HCO3- offering, and also affecting related signaling pathways. In addition, lncRNAs were found to crosstalk with miRNAs not only as primary competing endogenous RNAs but as the primary miRNAs. Our studies provided insight into non-coding RNA regulation of epigenetic regulation in biomineralization in bivalve species.
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Affiliation(s)
- Minxin Liang
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China
| | - Jinping Xie
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China
| | - Yiwei Huang
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China
| | - Qingheng Wang
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China; Pearl Breeding and Processing Engineering Technology Research Centre of Guangdong Province, Zhanjiang 524088, China; Guangdong Science and Innovation Center for Pearl Culture, Zhanjiang 524088, China; Guangdong Provincial Engineering Laboratory for Mariculture Organism Breeding, Zhanjiang 524088, China; Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Zhanjiang 524033, China
| | - Ronglian Huang
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China; Guangdong Provincial Engineering Laboratory for Mariculture Organism Breeding, Zhanjiang 524088, China; Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy culture, Zhanjiang 524088, China
| | - Yongshan Liao
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China; Guangdong Provincial Engineering Laboratory for Mariculture Organism Breeding, Zhanjiang 524088, China; Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Zhanjiang 524033, China
| | - Yuewen Deng
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China; Pearl Breeding and Processing Engineering Technology Research Centre of Guangdong Province, Zhanjiang 524088, China; Guangdong Science and Innovation Center for Pearl Culture, Zhanjiang 524088, China; Guangdong Provincial Engineering Laboratory for Mariculture Organism Breeding, Zhanjiang 524088, China; Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy culture, Zhanjiang 524088, China; Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Zhanjiang 524033, China
| | - Chuangye Yang
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China; Guangdong Provincial Engineering Laboratory for Mariculture Organism Breeding, Zhanjiang 524088, China; Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy culture, Zhanjiang 524088, China; Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Zhanjiang 524033, China
| | - Zhe Zheng
- Fishery collage, Guangdong Ocean University, 524088 Zhanjiang, China; Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy culture, Zhanjiang 524088, China; Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Zhanjiang 524033, China.
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Kazemi M, Sanati M, Shekari Khaniani M, Ghafouri-Fard S. A review on the lncRNA-miRNA-mRNA regulatory networks involved in inflammatory processes in Alzheimer's disease. Brain Res 2025; 1856:149595. [PMID: 40132722 DOI: 10.1016/j.brainres.2025.149595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/01/2025] [Accepted: 03/21/2025] [Indexed: 03/27/2025]
Abstract
Alzheimer's disease is a progressive neurodegenerative condition that is the most frequent reason for dementia. Due to the increasing trend of aging in societies, it will place a large social and financial burden on society. Although beta amyloid plaques and the formation of neurofibrillary tangles are mentioned as the main events in this disorder, the exact molecular pathology and inflammatory regulatory networks involved in neuroinflammatory events, as a fundamental pathogenic mechanism remain unknown. Understanding these molecular network pathways in addition to helping to understand the pathogenesis of Alzheimer's disease, can also help in the early diagnosis as well as the control of inflammatory processes that are involved in its progression. So, in this study, we intend to have an overview on the regulatory lncRNAs of Alzheimer's disease and their related miRNA and mRNAs, as well as the relationship of these regulatory pathways with inflammatory processes, so that we can provide a perspective for future studies in the field of diagnosis and possibly treatment of this disorder.
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Affiliation(s)
- Masoumeh Kazemi
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahla Sanati
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahmoud Shekari Khaniani
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Gholizadeh N, Yousefian M, Mohammadpour H, Razavi AE, Talaei S, Sheykhbahaei N. Long non-coding RNAs PVT1, CCAT2, and TCF7L2, and miR-33 and c-Myc expression in oral squamous cell carcinoma and oral lichen planus patients. J Craniomaxillofac Surg 2025:S1010-5182(25)00136-2. [PMID: 40360347 DOI: 10.1016/j.jcms.2025.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 03/09/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025] Open
Abstract
OBJECTIVE The objective of this study was to assess the potential of TCF7L2, CCAT2, and PVT1 LncRNAs, c-Myc, and miR-33 as biomarkers for early diagnosis and differentiation of oral squamous cell carcinoma (OSCC) and premalignant lesions. DESIGN Bioinformatics tools, including COSMIC, GeneMANIA, PathVisio, KEGG Pathway Database, IntOGen, and WikiPathways, were used to investigate the signaling pathways of cancer-associated genes. The limma package was utilized for statistical analysis to identify Differentially Expressed Genes (DEGs) between OSCC tumor and normal samples. The regulatory microRNAs were analyzed using miRDB, miRWalk, and TargetScan. The type of cancer for analysis was selected using IntOGen. The expression levels of LncRNAs, miR-33, and c-Myc were measured by polymerase chain reaction (PCR) in 28 OLP and 30 OSCC tissue samples, compared to 30 healthy and 30 OSCC-adjacent tissue specimens as control groups. Data were analyzed using the Mann-Whitney test, receiver operating characteristic (ROC) curve, and multiple linear regression. RESULTS The expression of c-Myc (3.53 ± 2.78 vs 0.93 ± 0.50), PVT1 (10.94 ± 8.49 vs 0.91 ± 0.48), CCAT2 (11.77 ± 10.00 vs 0.92 ± 0.95), and TCF7L2 (6.48 ± 4.30 vs 1.27 ± 0.96) was significantly higher in OSCC samples compared to OLP (P < 0.001). Conversely, miR-33 expression was significantly lower in OSCC samples (0.24 ± 0.25 vs 4.90 ± 3.90). There was a significant correlation between c-Myc, CCAT2, PVT1, and miR-33 expression and clinicopathological characteristics of OSCC specimens. In OSCC samples, c-Myc, PVT1, CCAT2, and TCF7L2 showed a significant positive correlation with each other, while miR-33 expression was negatively correlated with the overexpression of other genes. The area under the curve (AUC) for c-Myc, PVT-1, CCAT2, miR-33, and TCF7L2 were 0.917, 1.000, 0.979, 0.006, and 0.929, respectively. CONCLUSIONS Our findings suggest that c-Myc and LncRNAs (TCF7L2, PVT1, and CCAT2) are upregulated and miR-33 is downregulated in OSCC compared to OLP samples. These genes may serve as potential genetic biomarkers for diagnosis and prediction of clinicopathological features of OSCC.
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Affiliation(s)
- Narges Gholizadeh
- Department of Oral & Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Science, Tehran, Iran; Department of Oral & Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Yousefian
- Department of Oral & Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Science, Tehran, Iran
| | - Hadiseh Mohammadpour
- Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirnader Emami Razavi
- Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Sanam Talaei
- Department of Oral & Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Science, Tehran, Iran
| | - Nafiseh Sheykhbahaei
- Department of Oral & Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Science, Tehran, Iran.
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Kong L, Wang C, Lu X, Zhu Q, Song Y, Feng X. Novel cuproptosis-related lncRNAs risk model to predicting prognosis and guiding immunotherapy for OSCC patients. Discov Oncol 2025; 16:723. [PMID: 40349285 PMCID: PMC12066386 DOI: 10.1007/s12672-025-02578-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 05/05/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND A significant role in many cancers is played by cuproptosis, a new term for the copper-dependent regulatory cell death pattern. However, as a new research hotspot, the cuproptosis-related lncRNAs (CRLs) associated with regulation in oral squamous cell carcinoma (OSCC) patients are currently not well understood. METHODS Long noncoding RNA (lncRNA) data were downloaded from the Cancer Genome Atlas database (TCGA). The 'LIMMA' package in R software was used to screen for differential expression of CRLs. LASSO regression and COX regression models were used to construct prognostic signature based on 4 prognostic CRLs. Finally, the relationship of risk characteristics with immune correlation analysis, somatic mutations, PCA, biological molecular pathways and drug sensitivity was investigated. RESULTS A cuproptosis-related lncRNAs prognostic signature was developed by us. Based on the risk scores, the OSCC samples were split into high- and low-risk groups using this signature. The two risk groups differed significantly in immune functions, drug sensitivity, and overall survival. The risk model showed better prognostic predictive power compared to the traditional clinicopathological signature. By qPCR trial, we also verified the expression of STARD4-AS1 in OSCC cell lines and tissues was in line with our results from this experimental screen. Through cell experiments, we have confirmed that knocking down STARD4-AS1 promotes the proliferation and migration ability of OSCC cells. CONCLUSION The CRLs signature contributes to new understandings of the treatment of OSCC and is a rubost biomarker for predicting the prognosis of patients with OSCC.
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Affiliation(s)
- Lingbo Kong
- Wuxi Stomatological Hospital, Wuxi, Jiangsu, China
| | - Chenfei Wang
- Department of Stomatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China
| | - Xiaohui Lu
- Department of Stomatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China
| | - Qianqi Zhu
- Department of Stomatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China
- Medical School of Nantong University, Nantong, Jiangsu, China
| | - Yihua Song
- Department of Stomatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
- Medical School of Nantong University, Nantong, Jiangsu, China.
| | - Xingmei Feng
- Department of Stomatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
- Medical School of Nantong University, Nantong, Jiangsu, China.
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Zhu S, Liu Y, Chen H, Zhu X, Liu X, Xu K, Sang Y, Shang L, Chong W, Li L. Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer. Clin Med Insights Oncol 2025; 19:11795549251331755. [PMID: 40337354 PMCID: PMC12056339 DOI: 10.1177/11795549251331755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/13/2025] [Indexed: 05/09/2025] Open
Abstract
Serine hydroxymethyltransferase 2 (SHMT2) is a crucial mitochondrial enzyme in 1-carbon (1C) metabolism. It catalyzes the conversion of serine to glycine, generating 1C units essential for purine and pyrimidine synthesis, thereby supporting DNA replication and repair. Abnormally high expression is associated with malignant progression and treatment tolerance in various cancers. This review systematically summarizes the functions of SHMT2 in different types of cancer, underscoring on its roles in metabolism, immune microenvironment, and key signaling pathways (PI3K/AKT/mTOR, JAK-STAT, etc.) and outlines its epigenetic regulation and posttranslational modification mechanisms. Compared with the existing research, we focused on the latest regulatory mechanisms of SHMT2 and its potential in cancer treatment, such as the development and application of small-molecule inhibitors (SHIN2 and AGF347).
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Affiliation(s)
- Siqiang Zhu
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Yuan Liu
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Hao Chen
- Clinical Research Center of Shandong University, Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
| | - Xingyu Zhu
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Xinyu Liu
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Kang Xu
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Yaodong Sang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Wei Chong
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
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Zheng J, Mat Ludin AF, Rajab NF, Shaolong L, Jufri NF. The roles and signalling pathways of lncMALAT1 in coronary artery disease: A protocol for systematic review of in vivo and in vitro studies. PLoS One 2025; 20:e0322550. [PMID: 40323939 PMCID: PMC12052108 DOI: 10.1371/journal.pone.0322550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 03/17/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Coronary artery disease (CAD) is a major cardiovascular disease that affects global population health. Several studies have indicated the association between high expression level of a non-coding RNA, lncMALAT1 and an increased risk of CAD. In this study, we conducted a protocol of systematic review aims to evaluate the role and mechanism of lncMALAT1 that may contributed to CAD based on animal and in vitro studies. The roles of lncMALAT1 will be elucidated focusing on activating upstream signalling Klotho/FGF23 or regulate the downstream Wnt/β-catenin or extracellular signal-regulated kinase/mitogen-activated protein kinase(ERK/MAPK) and any other pathways with the vascular changes in term of proliferation, migration, lumen formation and apoptosis. METHODS A systematic review protocol with a reproducible strategy according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines and Population, Intervention, Comparison Outcome and Study (PICOS) framework were proposed to evaluate the existing literature on the roles and mechanisms of the lncMALAT1. A PRISMA-compliant electrical systematic research was performed in the databases including PubMed, Web of Science and Scopus for English publication from their inceptions until January 2024. Data for collection will include primary CAD animal models and any cardiomyocyte cell line with primary hypoxia model. The article title, authors, type of models, signaling pathways and biological changes (proliferation, migration, lumen formation and apoptosis) will be recorded. CONCLUSION This will provide a new approach in understanding molecular interactions on CAD for new perspective and target treatment for CAD patients in future, especially that intolerance of invasive coronary therapy. REGISTRATION Registered in PROSPERO on 10 April, 2024. (CRD42024504245) (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024504245).
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Affiliation(s)
- Jia Zheng
- Department of Cardiovascular Surgery, Yan’an Hospital affiliated to Kunming Medical University, Kunming, China
- Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Arimi Fitri Mat Ludin
- Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nor Fadilah Rajab
- Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Li Shaolong
- Department of Cardiology, Yan’an Hospital affiliated to Kunming Medical University, Kunming, China
| | - Nurul Farhana Jufri
- Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Tian Z, Cen L, Hua H, Wei F, Dong J, Huang Y, Wang Z, Deng J, Jiang Y. Prognostic and therapeutic potential of copper-induced cell death-related lncRNAs in lung squamous cell carcinoma. Clin Exp Med 2025; 25:135. [PMID: 40316808 PMCID: PMC12048434 DOI: 10.1007/s10238-025-01663-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 04/01/2025] [Indexed: 05/04/2025]
Abstract
Lung squamous cell carcinoma (LUSC), a major subtype of non-small cell lung cancer, remains challenging to treat due to poor prognosis and limited therapeutic options. This study investigates the prognostic and therapeutic implications of copper-induced cell death-related long non-coding RNAs (lncRNAs) in LUSC using data from The Cancer Genome Atlas. Five lncRNAs (AC010328.1, LINC01740, AL358613.2, MIR3945HG, AC002467.1) were identified as independent prognostic markers and incorporated into a risk score model to stratify patients into high- and low-risk groups. Survival analyses revealed significant differences in overall survival, with the high-risk group exhibiting higher immune evasion potential and poorer response to immunotherapy. Functional enrichment analyses highlighted the involvement of these lncRNAs in drug metabolism and tumor biology. Furthermore, tumor mutation burden analysis and immune dysfunction evaluation confirmed the clinical relevance of the model, identifying high-risk patients as more sensitive to targeted drugs such as Quizartinib and Dasatinib. A Nomogram integrating lncRNA risk scores and clinical factors demonstrated robust predictive accuracy for 1-, 3-, and 5-year survival outcomes. This study provides novel biomarkers and actionable insights for improving prognostic assessment and personalizing immunotherapy strategies for LUSC patients.
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Affiliation(s)
- Zhe Tian
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
| | - Lilan Cen
- Guangxi Academy of Medical Sciences, Department of Infectious Disease, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - Haoming Hua
- Department of Pathology, The Second People's Hospital of Bengbu, Bengbu, 233400, China
| | - Feng Wei
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
| | - Jue Dong
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
| | - Yulan Huang
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
| | - Zhibo Wang
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
| | - Junhua Deng
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China
| | - Yujie Jiang
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China.
- Life Science and Clinical Medicine Research Center, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2 Road, Youjiang District, Baise, 533000, Guangxi, China.
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10
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Li B, Li H, Cheng X, Fang Y, Liu Z, Zhao P, Jin L. Long non-coding RNA LINC01232 promotes malignancy of prostate cancer through regulation of miR-181a-5p/IRS2 pathway: Ki-67 protein molecular structure and function. Int J Biol Macromol 2025; 306:141817. [PMID: 40057086 DOI: 10.1016/j.ijbiomac.2025.141817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 02/20/2025] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
The expression level of long non-coding RNA (lncRNA), which functions in a manner similar to that of microrNA, has been confirmed to be closely associated with the regulatory network of multiple cancers. The primary focus of this particular research endeavor was to elucidate the mechanism of action of LINC01232 within the context of prostate cancer, specifically examining how it influences the proliferation of prostate cancer cells by interacting with the miR-181a-5p/IRS2 pathway. Additionally, the study aimed to delve deeper into the role of the Ki-67 protein within this intricate process. To assess the expression and localization of the Ki-67 protein in prostate cancer cells, researchers employed a combination of immunofluorescence and immunohistochemistry techniques. The expression level of Ki-67 protein decreased significantly after down-regulation of LINC01232, indicating that the cell proliferation activity was inhibited. Immunofluorescence and immunohistochemical experiments further confirmed that the expression of Ki-67 protein in prostate cancer cells was positively correlated with the expression of LINC01232.
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Affiliation(s)
- Baisen Li
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, China
| | - Huiying Li
- Outpatient Department of West China Hospital, Sichuan University, China
| | - Xiangming Cheng
- Department of Urology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China
| | - Yudong Fang
- Department of Vascular Diseases, Shanghai TCM-Integrated Hospital. No. 230 Baoding Road, Hongkou District, Shanghai 200082, China
| | - Zhe Liu
- Department of Vascular Diseases, Shanghai TCM-Integrated Hospital. No. 230 Baoding Road, Hongkou District, Shanghai 200082, China.
| | - Pei Zhao
- Department of Intensive Care Unit, Sichuan Cancer Hospital&Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China. 55# Renmin South Road, Wuhou District, Chengdu 610041, Sichuan, China.
| | - Li Jin
- School of Pharmacy, Faculty of Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, Macau University of Science and Technology, Macau 999078, China.
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11
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Yuan X, Yang L, Gao J, Wang B, Li Z. RNA modulation in asthma: unraveling the role of splicing and non-coding RNAs in disease pathogenesis. J Asthma 2025; 62:741-750. [PMID: 39688373 DOI: 10.1080/02770903.2024.2444305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 11/27/2024] [Accepted: 12/15/2024] [Indexed: 12/18/2024]
Abstract
OBJECTIVE To synthesize the current understanding of RNA-based regulatory mechanisms, focusing on how RNA splicing and non-coding RNAs shape immune responses and airway remodeling in asthma, with the aim of exploring their potential as therapeutic targets for asthma treatment. DATASOURCE Recent advances and emerging research in molecular biology and immunology related to RNA splicing, non-coding RNAs (lncRNAs, circRNAs), and N6-methyladenosine (m6A) RNA methylation in asthma pathogenesis. STUDY SELECTIONS The review incorporates studies highlighting the roles of alternative RNA splicing, non-coding RNAs (lncRNAs and circRNAs), and RNA methylation (m6A) in regulating immune and inflammatory pathways involved in asthma. RESULTS RNA splicing events, non-coding RNAs, and m6A RNA methylation are critical in modulating immune dysregulation, airway remodeling, and inflammation in asthma. These mechanisms influence key inflammatory pathways, mRNA stability, and the overall immune landscape of the disease. CONCLUSION RNA splicing and non-coding RNAs represent promising areas of research for understanding asthma's immune pathology and hold potential as novel therapeutic targets for more effective treatment strategies.
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Affiliation(s)
- Xingxing Yuan
- First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
| | - Liuxin Yang
- First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jiawei Gao
- First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Bingyu Wang
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
| | - Zhuying Li
- Department of Respiratory, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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12
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Ha J, Kim K. Neighborhood-Regularized Matrix Factorization for lncRNA-Disease Association Identification. Int J Mol Sci 2025; 26:4283. [PMID: 40362520 PMCID: PMC12072303 DOI: 10.3390/ijms26094283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
Long non-coding RNAs (lncRNAs) have been shown to be integral in a variety of biological processes and significantly influence the progression of several human diseases. Their involvement in disease mechanisms makes them crucial targets for research in disease biomarker identification. Understanding the intricate relationships between lncRNAs and diseases can offer valuable insights for advancing diagnostic, prognostic and therapeutic strategies. In light of this, we propose a recommendation-system-based model utilizing matrix factorization with disease neighborhood regularization to effectively infer disease-related lncRNAs (NRMFLDA). This approach leverages the power of matrix factorization techniques while incorporating disease neighborhood regularization to enhance the accuracy and reliability of lncRNA-disease association predictions. Consequently, NRMFLDA exhibits outstanding performance, achieving AUC scores of 0.9143 and 0.8993 in both leave-one-out and five-fold cross-validation, surpassing the performance of four previous models. This demonstrates its effectiveness and robustness in accurately predicting disease-related lncRNAs. We believe that NRMFLDA will not only provide innovative approaches for uncovering lncRNA-disease associations but also contribute significantly to the identification of novel biomarkers for various diseases, thereby advancing diagnostic and therapeutic strategies.
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Affiliation(s)
- Jihwan Ha
- Major of Big Data Convergence, Division of Data Information Science, Pukyong National University, Busan 48513, Republic of Korea;
| | - Kwangsu Kim
- Department of Scientific Computing, Pukyong National University, Busan 48513, Republic of Korea
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13
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Jiménez-Ortega RF, Aparicio-Bautista DI, Becerra-Cervera A, Ortega-Meléndez AI, Patiño N, Rivera-Paredez B, Hidalgo-Bravo A, Velázquez-Cruz R. The Regulatory Role of Long Non-Coding RNAs in the Development and Progression of Osteoporosis. Int J Mol Sci 2025; 26:4273. [PMID: 40362509 PMCID: PMC12072397 DOI: 10.3390/ijms26094273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 04/22/2025] [Accepted: 04/27/2025] [Indexed: 05/15/2025] Open
Abstract
Osteoporosis (OP) is a disease affecting bone metabolism, characterized by low bone mineral density and the deterioration of the bone microarchitecture, leading to increased bone fragility and risk of fracture. OP mainly results from alterations in the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Currently, there are several molecular mechanisms underlying the development of OP that are not entirely clear. One such mechanism is the role of long non-coding RNAs, which are key regulators of gene expression through various mechanisms. In the last decade, it has been shown that these molecules participate in multiple biological processes and play essential roles in the pathogenesis of different diseases. In this review, we address recent advances on the relationship of long non-coding RNAs with OP, mainly over their regulatory functions during osteoclastogenesis and osteogenesis. Furthermore, we analyze their potential application as clinical or therapeutic resources focused on OP.
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Affiliation(s)
- Rogelio F. Jiménez-Ortega
- Clínica Integral Universitaria (CIU), Universidad Estatal del Valle de Ecatepec (UNEVE), Ecatepec de Morelos 55210, Mexico;
- Programa Investigadoras e Investigadores, Consejo Mexiquense de Ciencia y Tecnología (COMECYT), Toluca 50120, Mexico
| | - Diana I. Aparicio-Bautista
- Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (D.I.A.-B.); (A.B.-C.)
| | - Adriana Becerra-Cervera
- Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (D.I.A.-B.); (A.B.-C.)
- Secretaría de Ciencias, Humanidades, Tecnología e Innovación (SECIHTI), Ciudad de México 03940, Mexico
| | - Alejandra I. Ortega-Meléndez
- Unidad Académica de Ciencias de la Salud, Universidad ETAC Campus Coacalco, Coacalco de Berriozábal 55700, Mexico;
| | - Nelly Patiño
- Unidad de Citometría de Flujo (UCiF), Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico;
| | - Berenice Rivera-Paredez
- Centro de Investigación en Políticas, Población y Salud, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico;
| | - Alberto Hidalgo-Bravo
- Departamento de Medicina Genómica, Instituto Nacional de Rehabilitación (INR), Mexico City 14389, Mexico;
| | - Rafael Velázquez-Cruz
- Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (D.I.A.-B.); (A.B.-C.)
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14
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Zhu T, Jiang W, Wu Y, Fang R, Deng F, Yang D. Advances in CRISPR/Cas13a-based biosensors for non-coding RNA detection. Talanta 2025; 294:128223. [PMID: 40300474 DOI: 10.1016/j.talanta.2025.128223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/29/2025] [Accepted: 04/24/2025] [Indexed: 05/01/2025]
Abstract
Non-coding RNAs play crucial roles in disease initiation and progression, making them promising biomarkers for early diagnosis and treatment monitoring. Conventional nucleic acid diagnostic methods, including polymerase chain reaction (PCR), next-generation sequencing (NGS), and enzyme-linked immunosorbent assay (ELISA), alongside emerging techniques such as single-molecule fluorescence in situ hybridization (smFISH), nanopore sequencing, and single-cell RNA sequencing (scRNA-seq), face inherent limitations in detecting regulatory non-coding RNAs. These challenges include laborious workflows, prolonged processing times, and technical complexities, hindering their broad applicability in rapid and high-throughput RNA analysis. CRISPR/Cas13a-based biosensors, integrated with various signal transduction systems-such as fluorescence, electrochemistry, colorimetry, surface-enhanced Raman spectroscopy (SERS)-show great promise for real-world diagnostic applications. This review provides a comprehensive overview of the CRISPR/Cas13a-mediated RNA detection mechanism, the development of CRISPR/Cas13a-based biosensors, and their integration with innovative signal detection methods. Additionally, we highlight the progress in portable detection devices, including lateral flow assay strips and smartphone-based platforms. Finally, the review discusses the current challenges and future prospects of CRISPR/Cas13a-based biosensors, particularly in the context of clinical diagnostics and personalized medicine.
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Affiliation(s)
- Tao Zhu
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, 315000, China
| | - Weiwei Jiang
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, 315000, China
| | - Yingyu Wu
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, 315000, China
| | - Rong Fang
- Ningbo Clinical and Pathological Diagnosis Center, Ningbo, 315000, China
| | - Fei Deng
- ARC Centre of Excellence in Nanoscale Biophotonics, University of New South Wales, Sydney, 2052, Australia
| | - Danting Yang
- Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, 315000, China.
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15
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Wen B, Chang W, Yang L, Lv D, Wang L, Wang L, Xu Y, Hu J, Ding K, Xue Q, Qi X, Yang B, Wang J. The long noncoding RNA APR attenuates PPRV infection-induced accumulation of intracellular iron to inhibit membrane lipid peroxidation and viral replication. mBio 2025; 16:e0012725. [PMID: 40126010 PMCID: PMC11980570 DOI: 10.1128/mbio.00127-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025] Open
Abstract
Peste des petits ruminants virus (PPRV) is an important pathogen that has long been a significant threat to small ruminant productivity worldwide. Iron metabolism is vital to the host and the pathogen. However, the mechanism underlying host-PPRV interactions from the perspective of iron metabolism and iron-mediated membrane lipid peroxidation has not been reported thus far. In this study, we identified a novel host long-noncoding RNA (lncRNA), APR, that impairs PPRV infectivity by sponging miR-3955-5p, a negative microRNA (miRNA) that directly targets the gene encoding the ferritin-heavy chain 1 (FTH1) protein. Importantly, we demonstrated that PPRV infection causes aberrant cellular iron accumulation by increasing transferrin receptor (TFRC) expression and that iron accumulation induces reticulophagy and ferroptosis, which benefits PPRV replication. Moreover, PPRV infection enhanced the localization of cellular iron on the endoplasmic reticulum (ER) and caused ER membrane damage by promoting excess lipid peroxidation to induce reticulophagy. Interestingly, APR decreased PPRV infection-induced accumulation of intracellular Fe2+ via miR-3955-5p/FTH1 axis and ultimately inhibited reticulophagy and ferroptosis. Additionally, our results indicate that interferon regulatory factor 1 promotes APR transcription by positively regulating APR promoter activity after PPRV infection. Taken together, our findings revealed a new pattern of PPRV-host interactions, involving noncoding RNA regulation, iron metabolism, and iron-related membrane lipid peroxidation, which is critical for understanding the host defense against PPRV infection and the pathogenesis of PPRV.IMPORTANCEMany viruses have been demonstrated to engage in iron metabolism to facilitate their replication and pathogenesis. However, the mechanism by which PPRV interacts with host cells from the perspective of iron metabolism, or iron-mediated membrane lipid peroxidation, has not yet been reported. Our data provide the first direct evidence that PPRV infection induces aberrant iron accumulation to promote viral replication and reveal a novel host lncRNA, APR, as a regulator of iron accumulation by promoting FTH1 protein expression. In this study, PPRV infection increased cellular iron accumulation by increasing TFRC expression, and more importantly, iron overload increased viral infectivity as well as promoted ER membrane lipid peroxidation by enhancing the localization of cellular iron on the ER and ultimately induced ferroptosis and reticulophagy. Furthermore, a host factor, the lncRNA APR, was found to decrease cellular iron accumulation by sponging miR-3955-5p, which directly targets the gene encoding the FTH1 protein, thereby attenuating PPRV infection-induced ferroptosis and reticulophagy and inhibiting PPRV infection. Taken together, the results of the present study provide new insight into our understanding of host-PPRV interaction and pathogenesis from the perspective of iron metabolism and reveal potential targets for therapeutics against PPRV infection.
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Affiliation(s)
- Bo Wen
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan, China
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
| | - Wenchi Chang
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
| | - Lulu Yang
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
| | - Daiyue Lv
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
- China Institute of Veterinary Drug Control, Beijing, Beijing, China
| | - Lizhen Wang
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
| | - Lei Wang
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan, China
| | - Yanzhao Xu
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan, China
| | - Jianhe Hu
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan, China
| | - Ke Ding
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan, China
| | - Qinghong Xue
- China Institute of Veterinary Drug Control, Beijing, Beijing, China
| | - Xuefeng Qi
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
| | - Bo Yang
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, China
| | - Jingyu Wang
- College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
- Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Xi'an, Shaanxi, China
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16
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Liu Q, Huang H, Zhang S, Liu F, Lou T. A novel cancer-associated lncRNA, LINC01123, participates in tumor progression, metabolism, immune escape, and resistance. Front Immunol 2025; 16:1480447. [PMID: 40255398 PMCID: PMC12006148 DOI: 10.3389/fimmu.2025.1480447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 03/17/2025] [Indexed: 04/22/2025] Open
Abstract
Long Intergenic Non-Protein Coding RNA 1123 (LINC01123), located on human chromosome 2q13, is a pivotal factor in tumorigenesis, exerting multifaceted oncogenic effects. Its expression strongly correlates with clinicopathological features, patient survival, and disease progression. In vivo and in vitro experiments further demonstrate that LINC01123 influences diverse cellular processes, including proliferation, apoptosis, viability, migration, invasion, stemness, and tumor growth. Notably, it also regulates metabolic reprogramming, immune escape, and tumor cell resistance to treatment. LINC01123 is regulated by multiple transcription factors and participates in gene regulation through protein interactions and competitive endogenous RNA (ceRNA) networks, thereby modulating cancer-promoting effects. This work systematically elucidates its primary functions and molecular mechanisms driving cancer initiation and progression, suggesting that LINC01123 might serve as a novel potential oncogenic driver and biomarker in various cancers.
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Affiliation(s)
- Qiang Liu
- Department of General Surgery, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, Jiangxi, China
| | - He Huang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Shuwen Zhang
- Queen Mary College, Nanchang University, Nanchang, Jiangxi, China
| | - Fangteng Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Ting Lou
- Department of Hospital Admission and Medical Record Management, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
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17
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Wei W, Zhang Z, Li B, Fu Z, Liu J. Deciphering the role of lncRNA-mediated ceRNA network in disuse osteoporosis: insights from bone marrow mesenchymal stem cells under simulated microgravity. Front Med (Lausanne) 2025; 12:1444165. [PMID: 40248073 PMCID: PMC12003301 DOI: 10.3389/fmed.2025.1444165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 03/17/2025] [Indexed: 04/19/2025] Open
Abstract
Background Disuse osteoporosis (DOP) poses a significant health risk during extended space missions. Although the importance of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cells (BMSCs) and orthopedic diseases is recognized, the precise mechanism by which lncRNAs contribute to DOP remains elusive. This research aims to elucidate the potential regulatory role of lncRNAs in DOP. Methods Sequencing data were obtained from Gene Expression Omnibus (GEO) datasets, including coding and non-coding RNAs. Positive co-expression pairs of lncRNA-mRNA were identified using weighted gene co-expression network analysis, while miRNA-mRNA expression pairs were derived from the prediction database. A mRNA-miRNA-lncRNA network was established according to the shared mRNA. Functional enrichment analysis was conducted for the shared mRNAs using genome ontology and KEGG pathways. Hub genes were identified through protein-protein interaction analysis, and connectivity map analysis was employed to identify potential therapeutic agents for DOP. Results Integration of 74 lncRNAs, 19 miRNAs, and 200 mRNAs yielded a comprehensive mRNA-miRNA-lncRNA network. Enrichment analysis highlighted endoplasmic reticulum stress and extracellular matrix (ECM) pathways as significant in the ceRNA network. PPI analysis revealed three hub genes (COL4A1, LAMC1, and LAMA4) and identified five lncRNA-miRNA-hub gene regulatory axes. Furthermore, three potential therapeutic compounds (SB-216763, oxymetholone, and flubendazole) for DOP were identified. Conclusion This study sheds light on the involvement of lncRNAs in the pathogenesis and treatment of DOP through the construction of a ceRNA network, linking protein-coding mRNA functions with non-coding RNAs.
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Affiliation(s)
- Wuzeng Wei
- Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China
- Clinical College of Orthopedics, Tianjin Medical University, Tianjin, China
| | - Zhongli Zhang
- Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China
- Clinical College of Orthopedics, Tianjin Medical University, Tianjin, China
| | - Bing Li
- Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China
- Clinical College of Orthopedics, Tianjin Medical University, Tianjin, China
| | - Zhe Fu
- Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China
- Clinical College of Orthopedics, Tianjin Medical University, Tianjin, China
| | - Jun Liu
- Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China
- Clinical College of Orthopedics, Tianjin Medical University, Tianjin, China
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18
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Wang D, Gao Y, Tan Y, Li N, Li X, Li J, Pan Y, Zhao X, Yan M, Wang Y. lncRNA Ubr5 promotes BMSCs apoptosis and inhibits their proliferation and osteogenic differentiation in weightless bone loss. Front Cell Dev Biol 2025; 13:1543929. [PMID: 40241795 PMCID: PMC11999945 DOI: 10.3389/fcell.2025.1543929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/10/2025] [Indexed: 04/18/2025] Open
Abstract
Background Weightless bone loss is a common pathological phenomenon in weightless environments, yet its specific molecular mechanism remain incompletely elucidated. The aim of this study was to systematically investigate the differential expression profiles of mRNAs and long noncoding RNAs (lncRNAs) to explore the molecular pathogenesis underlying weightless bone loss. Methods Transcriptome sequencing was performed on bone marrow mesenchymal stem cell (BMSCs) samples from the Ground control group and simulated microgravity (SMG) group using Illumina technology. Using the DESeq2 algorithm, we accurately identify and analyzed the differentially expressed genes (DEGs). Subsequently, the molecular functions and signaling pathways enriched by DEG were comprehensively analyzed by GO and KEGG. In addition, by constructing lncRNA-mRNA coexpression network, this study screened and verified key lncRNAs as potential genes to further explore their role in the occurrence and development of weightless bone loss. Results A total of 215 differentially expressed lncRNAs (DElncRNAs) and 381 differentially expressed mRNAs (DEmRNAs) were identified, in the SMG group. DEmRNAs were primarily involved in the cell response to mechanical stimulation, microtubule motility and TNF signaling pathway. Meanwhile, DElncRNAs are significantly enriched in cell differentiation, fatty acid metabolic process and biosynthesis of amino acids. In addition, the expression levels of related lncRNAs and mRNAs in weightless bone loss were verified via qRT-PCR. lncRNA-mRNA coexpression network found that lncRNA Ubr5 closely related to osteoblast proliferation and differentiation. Further experimental results revealed that knocking down lncRNA Ubr5 can promote the apoptosis of BMSCs and inhibit their proliferation and osteogenic differentiation. Conclusion This study revealed the molecular pathogenesis of weightless bone loss, identified lncRNA Ubr5 as a potential intervention target, and provided an important scientific basis and strategic guidance for the prevention and treatment of weightless bone loss.
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Affiliation(s)
- Dong Wang
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Yuan Gao
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Yingjun Tan
- State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Na Li
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Xi Li
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Jiaxiang Li
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Yikai Pan
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Xingcheng Zhao
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
| | - Ming Yan
- Department of Orthopedic Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Yongchun Wang
- Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an, China
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19
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Sharma NK, Mishra DC, Kumar B, Srivastava S, Chaturvedi KK, Singh AK, Madival SD, Budhlakoti N, Jha GK. Beyond the genome: unveiling tissue-specific non-coding RNAs in clove ( Syzygium aromaticum L.). 3 Biotech 2025; 15:81. [PMID: 40071125 PMCID: PMC11891123 DOI: 10.1007/s13205-025-04251-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Clove (Syzygium aromaticum), valued for its role in food preservation and medicine, has recently drawn research interest for its noncoding RNAs (ncRNAs). This study discovers 3274 long noncoding RNAs (lncRNAs) and 2404 circular RNAs (circRNAs) from publicly available RNAseq data. We identified the regulation of 834 genes through miRNA-lncRNA-mRNA network interactions. Additionally, 35 lncRNAs were predicted as precursors for 17 microRNAs (miRNAs), highlighting their role in post-transcriptional regulation. Tissue-specific analysis of circRNAs revealed their interaction with 1047 miRNAs and competing for binding sites on 2382 messenger RNAs (mRNAs). These results underscore their involvement in complex regulatory networks. To support further research and development, we developed SaroNcRDb (http://backlin.cabgrid.res.in/saroncrdb/), a web resource providing detailed insights into the types, chromosomal locations, tissue distributions, and interactions of identified ncRNAs. The findings pave the way for future studies to harness the regulatory roles of ncRNAs in improving Clove's agronomic traits and secondary metabolite production.
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Affiliation(s)
- Nitesh Kumar Sharma
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
- The Graduate School, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Dwijesh Chandra Mishra
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
- Department of Environmental and Public Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45221 USA
| | - Baibhav Kumar
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
- The Graduate School, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Sudhir Srivastava
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
| | - Krishna Kumar Chaturvedi
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
| | - Awani Kumar Singh
- Centre for Protected Cultivation Technology, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Sharanbasappa D. Madival
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
- The Graduate School, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Neeraj Budhlakoti
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
| | - Girish Kumar Jha
- Division of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
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20
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Gong L, Zhang H, Liu Y, Wang X, Xia R. Interactions Between Non-Coding RNAs and HIF-1alpha in the Context of Colorectal Cancer. Biomolecules 2025; 15:510. [PMID: 40305214 PMCID: PMC12024830 DOI: 10.3390/biom15040510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/17/2025] [Accepted: 03/30/2025] [Indexed: 05/02/2025] Open
Abstract
Hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular adaptation to hypoxia, drives colorectal cancer (CRC) progression by fueling angiogenesis, metastasis, and therapy resistance. Emerging evidence delineates intricate crosstalk between non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, and circular RNAs-and HIF-1α, forming bidirectional regulatory networks that orchestrate CRC pathogenesis. By interacting with HIF-1α, these non-coding RNAs contribute to the orchestration of the aggressive hypoxic tumor microenvironment. Recent studies have evaluated the clinical potential of lncRNAs and miRNAs in the realms of non-invasive liquid biopsies and RNA-targeted therapies. This review offers a comprehensive synthesis of recent investigations into the mechanisms by which lncRNAs and miRNAs interact with HIF-1α to modulate CRC progression. Additionally, we further explore the clinical implications of ncRNA/HIF-1α crosstalk, emphasizing their potential as diagnostic biomarkers and therapeutic targets, while also spotlighting intriguing and promising areas of ncRNA research. Methods: In this study, our search strategy employed in databases such as PubMed, Web of Science, and EMBASE is as follows: we will specify search terms, including combinations of "non-coding RNA", "HIF-1α", and "colorectal cancer", along with a date range for the literature search (for example, from 2000 to 2025) to capture the most relevant and up-to-date research.
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Affiliation(s)
| | | | | | - Xianwang Wang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China; (L.G.); (H.Z.); (Y.L.)
| | - Ruohan Xia
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China; (L.G.); (H.Z.); (Y.L.)
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21
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Su F, Dolmatov IY, Wang T, Yang H, Ding K, Zhang L, Sun L. LncRNA-miRNA interplay regulate intestinal regeneration in the sea cucumber Apostichopus japonicus. Comput Struct Biotechnol J 2025; 27:1383-1393. [PMID: 40235637 PMCID: PMC11999485 DOI: 10.1016/j.csbj.2025.03.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/19/2025] [Accepted: 03/28/2025] [Indexed: 04/17/2025] Open
Abstract
The sea cucumber Apostichopus japonicus, renowned for its remarkable ability to expel and regenerate its internal organs within weeks, serves as a model organism for regeneration research. However, studies on the role of non-coding RNAs, particularly long non-coding RNA (lncRNA), in intestinal regeneration remain limited. In this study, we identified and performed differential expression analysis of lncRNAs in both normal intestines and intestines at 3 days post evisceration (dpe). A total of 2361 lncRNAs were identified, 183 of which were differentially expressed (DE-lncRNAs). The genes targeted by these lncRNAs, either cis- or trans-acting, were involved in oxidative stress, immune response, extracellular matrix remodeling, and energy metabolism during intestinal regeneration. Notably, MSTRG.6200/miR-7847-3p and MSTRG.18440/miR-4220-5p have been confirmed as interacting lncRNA-miRNA pairs. These results suggest that lncRNAs are key regulators of intestinal regeneration in A. japonicus, offering new insights into the underlying mechanisms and potential targets for enhancing regeneration.
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Affiliation(s)
- Fang Su
- CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture (CAS), Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Igor Yu. Dolmatov
- A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Vladivostok 690041, Russia
| | - Tianming Wang
- National Engineering Laboratory of Marine Germplasm Resources Exploration and Utilization, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan 316022, China
| | - Hongsheng Yang
- CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture (CAS), Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Kui Ding
- CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
| | - Libin Zhang
- CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture (CAS), Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lina Sun
- CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao 266237, China
- Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture (CAS), Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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22
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Agris PF. Targeting Gene Transcription Prevents Antibiotic Resistance. Antibiotics (Basel) 2025; 14:345. [PMID: 40298535 PMCID: PMC12024381 DOI: 10.3390/antibiotics14040345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/07/2025] [Accepted: 03/18/2025] [Indexed: 04/30/2025] Open
Abstract
Innovative strategies are needed to curb the global health challenge of antibiotic resistance. The World Health Organization predicts that antibiotic resistance could lead to millions of deaths annually. Pharmaceutical experience has shown that modest alterations of commonly-used broad-spectrum antibiotics readily elicit resistant strains. Thus, continued simple iterative improvements on current antibiotics are not sustainable. Traditional strategies target single sites with the goal of a broad-spectrum antibiotic. In comparison, a novel strategy targets multiple sites in single- or multidrug-resistant Gram-positive bacterial pathogens. The objective is to exploit the mechanisms by which pathogenic bacteria require genes for transcriptional regulation. Transcription regulatory factors can be manipulated and their functions disrupted to hamper bacterial viability. Some transcription factors regulate one or more steps in metabolic pathways. Transcription factors are not always proteins; some are small-molecule metabolites triggering genetic functions through riboswitches, and others are RNAs. Novel agents have been discovered with computer-simulated docking to an unusual transcription regulatory site in nascent bacterial mRNA. These compounds exhibit innovative chemistries and modes of action that inhibit bacterial growth by binding to and blocking critical Gram-positive mRNA functions. The tRNA-dependent transcription regulation of amino acid metabolism illustrates the possibilities of novel strategies to inhibit antibiotic-resistant growth and thwart the emergence of novel resistant strains.
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Affiliation(s)
- Paul F Agris
- Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
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23
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Li J, Dong Z, Tang L, Liu L, Su C, Yu S. Long Non-coding RNA MIR22HG Alleviates Ischemic Acute Kidney Injury by Targeting the miR-134-5p/NFAT5 axis. Inflammation 2025:10.1007/s10753-025-02286-5. [PMID: 40095256 DOI: 10.1007/s10753-025-02286-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 03/02/2025] [Accepted: 03/04/2025] [Indexed: 03/19/2025]
Abstract
Acute kidney injury (AKI), often triggered by ischemia-reperfusion (I/R) injury, is a critical condition characterized by rapid loss of renal function, leading to high morbidity and mortality. Despite extensive research, therapeutic options for ischemic AKI remain limited, and understanding the molecular mechanisms involved is crucial for developing targeted therapies. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various diseases, including cancer and renal injury. This study investigates the role of the lncRNA MIR22HG in mitigating renal injury during ischemic AKI. Using in vivo and in vitro models of I/R-induced AKI in mice and hypoxia/reoxygenation (H/R)-treated renal cells, we demonstrated that MIR22HG expression is significantly downregulated in ischemic AKI conditions. Functional assays showed that overexpression of MIR22HG in these models led to reduced renal cell apoptosis, inflammation, and improved renal function. Mechanistically, MIR22HG exerted its protective effects by negatively regulating miR-134-5p, which in turn alleviated renal injury by upregulating NFAT5, a transcription factor known to mitigate cellular stress. Furthermore, dual-luciferase and RNA pull-down assays confirmed direct interactions between MIR22HG and miR-134-5p, as well as miR-134-5p and NFAT5. Additionally, loss-and-gain-of-function assays demonstrated that overexpression of MIR22HG led to the upregulation of NFAT5, which mitigated renal apoptosis, and inflammation and improved renal function. Collectively, the results of our study highlight the therapeutic potential of targeting the MIR22HG/miR-134-5p/NFAT5 axis in the treatment of ischemic AKI, providing new insights into the molecular regulation of renal cell survival and repair during injury.
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Affiliation(s)
- Jingdong Li
- Department of Emergency and Disaster Medical Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China
| | - Zhe Dong
- Department of Critical Care Medicine, Shenyang Fourth People's Hospital, Shenyang, 110083, Liaoning, China
| | - Liting Tang
- Department of Critical Care Medicine, Shenyang Fourth People's Hospital, Shenyang, 110083, Liaoning, China
| | - Lu Liu
- Department of Critical Care Medicine, Shenyang Fourth People's Hospital, Shenyang, 110083, Liaoning, China
| | - Cuijing Su
- Department of Emergency, Shenyang Sujiatun District Central Hospital, Shenyang , 110100, Liaoning, China
| | - Shan Yu
- Department of General Medicine, The Seventh Affiliated Hospital of Sun Yat-Sen University, No. 628, Zhenyuan Road, Xinhu Street, Guangming District, Shenzhen, 518107, Guangdong, China.
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24
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Liu Q. Role of exercise on the reduction of cancer development: a mechanistic review from the lncRNA point of view. Clin Exp Med 2025; 25:77. [PMID: 40063304 PMCID: PMC11893680 DOI: 10.1007/s10238-025-01618-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 02/26/2025] [Indexed: 03/14/2025]
Abstract
More research has been done on the correlation between exercise and cancer, which has revealed several ways that physical activity decreases the risk of developing the disease. The developing function of lncRNAs as an important molecular link between exercise and cancer suppression is the main topic of this review. According to recent research, regular physical exercise also alters the expression levels of several lncRNAs, which are generally elevated in cancer. A complex network of interactions that may provide protective effects against carcinogenesis is suggested by the contribution of these lncRNAs in various cellular processes, such as epigenetic alterations, proliferation, and apoptosis regulation. We offer a comprehensive summary of the existing information regarding specific lncRNAs that are influenced by physical activity and could potentially impact cancer-related processes. We also go over the difficulties in interpreting these alterations, taking into account the fact that several lncRNAs have a dual function in promoting and preventing cancer in various physiological settings. To understand the complex impacts of exercise-induced lncRNA regulation in cancer biology, more study is required. The critique strongly highlights the possibility of lncRNAs serving as both indicators and treatment prospects for cancer-preventive strategies.
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Affiliation(s)
- Qi Liu
- Nanchang Institute of Technology, Nanchang, 330044, China.
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25
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Deng L, Gòdia M, Derks MFL, Harlizius B, Farhangi S, Tang Z, Groenen MAM, Madsen O. Comprehensive expression genome-wide association study of long non-coding RNAs in four porcine tissues. Genomics 2025; 117:111026. [PMID: 40049421 DOI: 10.1016/j.ygeno.2025.111026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 02/27/2025] [Accepted: 03/03/2025] [Indexed: 03/10/2025]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs), a type of non-coding RNA molecules, are known to play critical regulatory roles in various biological processes. However, the functions of the majority of lncRNAs remain largely unknown, and little is understood about the regulation of lncRNA expression. In this study, high-throughput DNA genotyping and RNA sequencing were applied to investigate genomic regions associated with lncRNA expression, commonly referred to as lncRNA expression quantitative trait loci (eQTLs). We analyzed the liver, lung, spleen, and muscle transcriptomes of 100 three-way crossbred sows to identify lncRNA transcripts, explore genomic regions that might influence lncRNA expression, and identify potential regulators interacting with these regions. RESULT We identified 6380 lncRNA transcripts and 3733 lncRNA genes. Correlation tests between the expression of lncRNAs and protein-coding genes were performed. Subsequently, functional enrichment analyses were carried out on protein-coding genes highly correlated with lncRNAs. Our correlation results of these protein-coding genes uncovered terms that are related to tissue specific functions. Additionally, heatmaps of lncRNAs and protein-coding genes at different correlation levels revealed several distinct clusters. An expression genome-wide association study (eGWAS) was conducted using 535,896 genotypes and 1829, 1944, 2089, and 2074 expressed lncRNA genes for liver, spleen, lung, and muscle, respectively. This analysis identified 520,562 significant associations and 6654, 4525, 4842, and 7125 eQTLs for the respective tissues. Only a small portion of these eQTLs were classified as cis-eQTLs. Fifteen regions with the highest eQTL density were selected as eGWAS hotspots and potential mechanisms of lncRNA regulation in these hotspots were explored. However, we did not identify any interactions between the transcription factors or miRNAs in the hotspots and the lncRNAs, nor did we observe a significant enrichment of regulatory elements in these hotspots. While we could not pinpoint the key factors regulating lncRNA expression, our results suggest that the regulation of lncRNAs involves more complex mechanisms. CONCLUSION Our findings provide insights into several features and potential functions of lncRNAs in various tissues. However, the mechanisms by which lncRNA eQTLs regulate lncRNA expression remain unclear. Further research is needed to explore the regulation of lncRNA expression and the mechanisms underlying lncRNA interactions with small molecules and regulatory proteins.
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Affiliation(s)
- Liyan Deng
- Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands; Kunpeng Institute of Modern Agriculture at Foshan, Agricultural Genomics Institute, Chinese Academy of Agricultural Sciences, Foshan 528226, China; Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
| | - Marta Gòdia
- Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
| | - Martijn F L Derks
- Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands; Topigs Norsvin Research Center, 's-Hertogenbosch, the Netherlands
| | | | - Samin Farhangi
- Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
| | - Zhonglin Tang
- Kunpeng Institute of Modern Agriculture at Foshan, Agricultural Genomics Institute, Chinese Academy of Agricultural Sciences, Foshan 528226, China; Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China
| | - Martien A M Groenen
- Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands
| | - Ole Madsen
- Animal Breeding and Genomics, Wageningen University & Research, Wageningen, the Netherlands.
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26
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Chanda S, Roy J, Banu N, Poudel A, Phogat S, Hossain F, Muthusamy V, Gaikwad K, Mandal PK, Madhavan J. A detailed comparative in silico and functional analysis of ccd1 gene in maize gives new insights of its expression and functions. Mol Biol Rep 2025; 52:279. [PMID: 40035960 DOI: 10.1007/s11033-025-10378-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 02/25/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND Biofortified maize with enhanced carotenoid content was developed to combat vitamin A deficiency. However, it was observed that during storage, carotenoids present in maize grain get degraded and it has been reported that carotenoid cleavage dioxygenase1 (ccd1) is responsible for this degradation. METHODS AND RESULTS In our current study, comprehensive in-silico analysis deciphered a complete overview of the ccd1 gene in maize including the gene structures, phylogeny, chromosomal locations, promoter analysis, conserved motifs and interacting protein partners. In addition to these, a comparative in-silico analysis of the ccd1 gene in maize, rice and Arabidopsis was performed. An intronic region of ccd1, unique to the maize genome, was matched significantly with a lot of long non-coding RNA and was identified. Also, growth stage-specific ccd1 expression analysis was performed in two maize inbred lines, V335PV and HKI161PV. The results indicate that both inbred lines displayed higher ccd1 expression during reproductive stages compared to vegetative stages, with the highest expression level observed at the milking stage in both inbreds. CONCLUSION This detailed in-silico characterisation and expression analysis of the ccd1 gene contributes to our understanding of its activity and expression pattern in maize in stage and tissue-specific manner. This study will further provide an effective strategy for manipulating the ccd1 gene to enhance the carotenoid content of maize grain, thereby aiding in the combat against vitamin A deficiency.
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Affiliation(s)
- Sagnik Chanda
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India
- Division of Molecular Biology and Biotechnology, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Jeet Roy
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India
- Division of Molecular Biology and Biotechnology, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Nuzat Banu
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India
- Division of Molecular Biology and Biotechnology, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Ankur Poudel
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India
- Division of Molecular Biology and Biotechnology, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Sachin Phogat
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India
- Division of Molecular Biology and Biotechnology, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Firoz Hossain
- Division of Genetics, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Vignesh Muthusamy
- Division of Genetics, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India
| | - Kishor Gaikwad
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India
| | - Pranab Kumar Mandal
- Indian Council of Agricultural Research-National Institute for Plant Biotechnology (ICAR-NIPB), LBS Building, Pusa Campus, New Delhi, 110012, India.
| | - Jayanthi Madhavan
- Division of Genetics, ICAR-Indian Agricultural Research Institute (ICAR-IARI), New Delhi, India.
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27
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Dos Santos TCF, Silva EN, Frezarim GB, Salatta BM, Baldi F, Fonseca LFS, Albuquerque LGD, Muniz MMM, Silva DBDS. Identification of cis-sQTL demonstrates genetic associations and functional implications of inflammatory processes in Nelore cattle muscle tissue. Mamm Genome 2025; 36:106-117. [PMID: 39825903 DOI: 10.1007/s00335-024-10100-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/22/2024] [Indexed: 01/20/2025]
Abstract
This study aimed to identify splicing quantitative trait loci (cis-sQTL) in Nelore cattle muscle tissue and explore the involvement of spliced genes (sGenes) in immune system-related biological processes. Genotypic data from 80 intact male Nelore cattle were obtained using SNP-Chip technology, while RNA-Seq analysis was performed to measure gene expression levels, enabling the integration of genomic and transcriptomic datasets. The normalized expression levels of spliced transcripts were associated with single nucleotide polymorphisms (SNPs) through an analysis of variance using an additive linear model with the MatrixEQTL package. A permutation analysis then assessed the significance of the best SNPs for each spliced transcript. Functional enrichment analysis was performed on the sGenes to investigate their roles in the immune system. In total, 3,187 variants were linked to 3,202 spliced transcripts, with 83 sGenes involved in immune system processes. Of these, 31 sGenes were enriched for five transcription factors. Most cis-sQTL effects were found in intronic regions, with 27 sQTL variants associated with disease susceptibility and resistance in cattle. Key sGenes identified, such as GSDMA, NLRP6, CASP6, GZMA, CASP4, CASP1, TREM2, NLRP1, and NAIP, were related to inflammasome formation and pyroptosis. Additionally, genes like PIDD1, OPTN, NFKBIB, STAT1, TNIP3, and TREM2 were involved in regulating the NF-kB pathway. These findings lay the groundwork for breeding disease-resistant cattle and enhance our understanding of genetic mechanisms in immune responses.
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Affiliation(s)
- Thaís Cristina Ferreira Dos Santos
- Universidade Professor Edson Antônio Velano (UNIFENAS), Rodovia 179, Km 0, Alfenas, MG, 37132440, Brasil.
- Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP, Brasil.
| | - Evandro Neves Silva
- Universidade Professor Edson Antônio Velano (UNIFENAS), Rodovia 179, Km 0, Alfenas, MG, 37132440, Brasil
- Universidade Federal de Alfenas (UNIFAL), Alfenas, MG, Brasil
| | | | - Bruna Maria Salatta
- Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP), Jaboticabal, SP, Brasil
| | - Fernando Baldi
- Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP), Jaboticabal, SP, Brasil
| | | | - Lucia Galvão De Albuquerque
- Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP), Jaboticabal, SP, Brasil
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, DF, Brasil
| | - Maria Malane Magalhães Muniz
- Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP), Jaboticabal, SP, Brasil
- University of Guelph, UOGELPH, Guelph, Canada
| | - Danielly Beraldo Dos Santos Silva
- Universidade Professor Edson Antônio Velano (UNIFENAS), Rodovia 179, Km 0, Alfenas, MG, 37132440, Brasil.
- Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP), Jaboticabal, SP, Brasil.
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Olatunji M, Liu Y. RNA damage and its implications in genome stability. DNA Repair (Amst) 2025; 147:103821. [PMID: 40043352 DOI: 10.1016/j.dnarep.2025.103821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 02/19/2025] [Accepted: 02/25/2025] [Indexed: 03/17/2025]
Abstract
Endogenous and environmental stressors can damage DNA and RNA to compromise genome and transcriptome stability and integrity in cells, leading to genetic instability and diseases. Recent studies have demonstrated that RNA damage can also modulate genome stability via RNA-templated DNA synthesis, suggesting that it is essential to maintain RNA integrity for the sustainment of genome stability. However, little is known about RNA damage and repair and their roles in modulating genome stability. Current efforts have mainly focused on revealing RNA surveillance pathways that detect and degrade damaged RNA, while the critical role of RNA repair is often overlooked. Due to their abundance and susceptibility to nucleobase damaging agents, it is essential for cells to evolve robust RNA repair mechanisms that can remove RNA damage, maintaining RNA integrity during gene transcription. This is supported by the discovery of the alkylated RNA nucleobase repair enzyme human AlkB homolog 3 that can directly remove the methyl group on damaged RNA nucleobases, predominantly in the nucleus of human cells, thereby restoring the integrity of the damaged RNA nucleobases. This is further supported by the fact that several DNA repair enzymes can also process RNA damage. In this review, we discuss RNA damage and its effects on cellular function, DNA repair, genome instability, and potential RNA damage repair mechanisms. Our review underscores the necessity for future research on RNA damage and repair and their essential roles in modulating genome stability.
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Affiliation(s)
- Mustapha Olatunji
- Biochemistry Ph.D. Program, Florida International University, Miami, FL, USA
| | - Yuan Liu
- Biochemistry Ph.D. Program, Florida International University, Miami, FL, USA; Department of Chemistry and Biochemistry, and Florida International University, Miami, FL, USA; Biomolecular Sciences Institute, Florida International University, Miami, FL, USA.
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Cornelissen FMG, He Z, Ciputra E, de Haas RR, Beumer‐Chuwonpad A, Noske D, Vandertop WP, Piersma SR, Jiménez CR, Murre C, Westerman BA. The translatome of glioblastoma. Mol Oncol 2025; 19:716-740. [PMID: 39417309 PMCID: PMC11887679 DOI: 10.1002/1878-0261.13743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 07/17/2024] [Accepted: 07/19/2024] [Indexed: 10/19/2024] Open
Abstract
Glioblastoma (GB), the most common and aggressive brain tumor, demonstrates intrinsic resistance to current therapies, resulting in poor clinical outcomes. Cancer progression can be partially attributed to the deregulation of protein translation mechanisms that drive cancer cell growth. In this study, we present the translatome landscape of GB as a valuable data resource. Eight patient-derived GB sphere cultures (GSCs) were analyzed using ribosome profiling and messenger RNA (mRNA) sequencing. We investigated inter-cell-line differences through differential expression analysis at both the translatome and transcriptome levels. Translational changes post-radiotherapy were assessed at 30 and 60 min. The translation of non-coding RNAs (ncRNAs) was validated using in-house and public mass spectrometry (MS) data, whereas RNA expression was confirmed by quantitative PCR (qPCR). Our findings demonstrate that ribosome sequencing provides more detailed information than MS or transcriptional analyses. Transcriptional similarities among GSCs correlate with translational similarities, aligning with previously defined subtypes such as proneural and mesenchymal. Additionally, we identified a broad spectrum of open reading frame types in both coding and non-coding mRNA regions, including long non-coding RNAs (lncRNAs) and pseudogenes undergoing active translation. Translation of ncRNAs into peptides was independently confirmed by in-house data and external MS data. We also observed that translational regulation of histones (downregulated) and splicing factors (upregulated) occurs in response to radiotherapy. These data offer new insights into genome-wide protein synthesis, identifying translationally regulated genes and alternative translation initiation sites in GB under normal and radiotherapeutic conditions, providing a rich resource for GB research. Further functional validation of differentially expressed genes after radiotherapy is needed. Understanding translational control in GB can reveal mechanistic insights and identify currently unknown biomarkers, ultimately enhancing the diagnosis and treatment of this aggressive brain cancer.
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Affiliation(s)
- Fleur M. G. Cornelissen
- Department of Molecular BiologyUniversity of California, San DiegoLa JollaCAUSA
- Department of NeurosurgeryAmsterdam UMC, Location VUMC, Cancer CenterAmsterdamThe Netherlands
| | - Zhaoren He
- Department of Molecular BiologyUniversity of California, San DiegoLa JollaCAUSA
| | - Edward Ciputra
- Department of NeurosurgeryAmsterdam UMC, Location VUMC, Cancer CenterAmsterdamThe Netherlands
| | - Richard R. de Haas
- OncoProteomics Laboratory, Cancer Center AmsterdamAmsterdam UMCThe Netherlands
| | | | - David Noske
- Department of NeurosurgeryAmsterdam UMC, Location VUMC, Cancer CenterAmsterdamThe Netherlands
| | - W. Peter Vandertop
- Department of NeurosurgeryAmsterdam UMC, Location VUMC, Cancer CenterAmsterdamThe Netherlands
| | - Sander R. Piersma
- OncoProteomics Laboratory, Cancer Center AmsterdamAmsterdam UMCThe Netherlands
| | - Connie R. Jiménez
- OncoProteomics Laboratory, Cancer Center AmsterdamAmsterdam UMCThe Netherlands
| | - Cornelis Murre
- Department of Molecular BiologyUniversity of California, San DiegoLa JollaCAUSA
| | - Bart A. Westerman
- Department of NeurosurgeryAmsterdam UMC, Location VUMC, Cancer CenterAmsterdamThe Netherlands
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Hu X, Wang D, Chen J, Liang B, Zhang L, Qin P, Wu D. The role of lnc‑MAPKAPK5‑AS1 in immune cell infiltration in hepatocellular carcinoma: Bioinformatics analysis and validation. Oncol Lett 2025; 29:141. [PMID: 39850723 PMCID: PMC11755229 DOI: 10.3892/ol.2025.14887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 11/18/2024] [Indexed: 01/25/2025] Open
Abstract
The oncogenic and tumor suppressor roles of lnc-MAPKAPK5-AS1 in multiple cancers suggest its complexity in modulating cancer progression. The expression and promoter methylation level of lnc-MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) was investigated through data mining from The Cancer Genome Atlas and Gene Expression Omnibus and its significance in prognosis and immunity was explored. lnc-MAPKAPK5-AS1 was co-expressed with its protein-coding gene MAPKAPK5 in HCC and exhibited upregulation in HCC tissues as a result of hypomethylation of its promoter region. High expression of lnc-MAPKAPK5-AS1 was associated with poor prognosis. Enrichment analysis revealed that lnc-MAPKAPK5-AS1 is involved in immune and metabolic-related pathways. Changes in the expression of lnc-MAPKAPK5-AS1 affected plasma cells, T cells CD4+ memory resting, NK cells, macrophages M0/M1, and mast cells resting in the tumor microenvironment. lnc-MAPKAPK5-AS1 was found to correlate with multiple immune checkpoints. Analysis of the Sangerbox database revealed positive relationships between expression of lnc-MAPKAPK5-AS1, tumor mutational burden and microsatellite instability, which suggested that immunotherapy may be effective in tumors with high expression of lnc-MAPKAPK5-AS1. The expression of lnc-MAPKAPK5-AS1 was verified to indicate sensitivity to 16 common targeted drugs. Immunohistochemistry confirmed the expression of MAPKAPK5 protein in HCC and its prognostic significance. Weighted gene co-expression network analysis was applied to identify hub genes related to both immunoreactive score and gene expression. These results revealed that lnc-MAPKAPK5-AS1 may be involved in the occurrence and development of HCC as an oncogene and may represent a potential therapeutic target through modulating the substance metabolism and immune response.
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Affiliation(s)
- Xiangzhi Hu
- Guangzhou Center for Disease Control and Prevention, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
- Infectious Disease Control Department, Yidu Center for Disease Control and Prevention, Yidu, Hubei 443300, P.R. China
| | - Dedong Wang
- Guangzhou Center for Disease Control and Prevention, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
| | - Jinbin Chen
- Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Boheng Liang
- Guangzhou Center for Disease Control and Prevention, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
| | - Lin Zhang
- Guangzhou Center for Disease Control and Prevention, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
| | - Pengzhe Qin
- Guangzhou Center for Disease Control and Prevention, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
| | - Di Wu
- Guangzhou Center for Disease Control and Prevention, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
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Li Y, Li Q, Wang X, Zhang J, Yan S, Shen B, Qi P, Li H. Comprehensive transcriptome analysis reveals lncRNA-mRNA interactions and immune response mechanisms in Mytilus coruscus upon Vibrio alginolyticus infection. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2025; 164:105327. [PMID: 39884369 DOI: 10.1016/j.dci.2025.105327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 02/01/2025]
Abstract
Long non-coding RNAs (lncRNAs) play diverse biological roles within cells. Despite not encoding proteins, they are crucial in regulating gene expression, chromatin structure and function, cell differentiation and development, and the occurrence of diseases. Vibrio alginolyticus (V. alginolyticus) is a common bacterium found in marine environments that poses a threat to shellfish by infecting them through filtration feeding. Research has demonstrated the substantial involvement of lncRNAs in the immune response of shellfish. However, the specific mechanism by which lncRNAs participate in the immune regulatory process following infection of Mytilus coruscus (M. coruscus) with V. alginolyticus has not been investigated. Therefore, the transcription profiles of lncRNAs in M. coruscus hemocytes were investigated. A grand total of 48,246 lncRNAs were detected, with 2421 genes that exhibited and 717 lncRNAs that had differential expression. To gain a better understanding of the potential roles of the differentially expressed lncRNAs (DE-lncRNAs), GO and KEGG pathway analyses were performed on their target mRNAs, suggesting that lncRNAs have the ability to control gene expression levels and consequently influence immune-related pathways, hence regulating the immune response in M. coruscus. Additionally, a total of 138 lncRNA-mRNA pairs were identified through the calculation of co-expression relationships between DE-lncRNAs and immune-related DE-mRNAs. These findings provide new insights into the role of lncRNAs in the immune response of M. coruscus and offer important resources for further investigation into the role of lncRNAs in M. coruscus pathogen infection.
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Affiliation(s)
- Yaru Li
- National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang, 316004, China
| | - Qingyang Li
- Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China; Harbin Medical University, 157 Baojian Road, Harbin, 150081, China
| | - Xiaoya Wang
- National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang, 316004, China
| | - Jingyan Zhang
- Ocean College, Zhejiang University, Zhoushan, 316021, China
| | - Shuang Yan
- Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China; Harbin Medical University, 157 Baojian Road, Harbin, 150081, China
| | - Bin Shen
- National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang, 316004, China
| | - Pengzhi Qi
- National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang, 316004, China
| | - Hongfei Li
- National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, Zhejiang, 316004, China.
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Zhu J, Jian Z, Liu F, Le L. The emerging landscape of small nucleolar RNA host gene 10 in cancer mechanistic insights and clinical relevance. Cell Signal 2025; 127:111590. [PMID: 39798772 DOI: 10.1016/j.cellsig.2025.111590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/14/2024] [Accepted: 01/03/2025] [Indexed: 01/15/2025]
Abstract
Small nucleolar RNA host gene 10 (SNHG10) is a newly recognized long non-coding RNA (lncRNA) with significant implications in cancer biology. Abnormal expression of SNHG10 has been observed in various solid tumors and hematological malignancies. Research conducted in vivo and in vitro has revealed that SNHG10 plays a pivotal role in numerous biological processes, including cell proliferation, apoptosis, invasion and migration, drug resistance, energy metabolism, immune evasion, as well as tumor growth and metastasis. SNHG10 regulates tumor development through several mechanisms, such as competing with microRNA (miRNA) for binding sites, modulating various signaling pathways, influencing transcriptional activity, and affecting epigenetic regulation. The diverse biological functions and intricate mechanisms of SNHG10 highlight its considerable clinical relevance, positioning it as a potential pan-cancer biomarker and therapeutic target. This review aims to summarize the role of SNHG10 in tumorigenesis and cancer progression, clarify the molecular mechanisms at play, and explore its clinical significance in cancer diagnosis and prognosis prediction, along with its therapeutic potential.
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Affiliation(s)
- Jingyu Zhu
- Second Clinical Medical School, Nanchang University, Nanchang, Jiangxi, China
| | - Zihao Jian
- Second Clinical Medical School, Nanchang University, Nanchang, Jiangxi, China
| | - Fangteng Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, Jiangxi, China.
| | - Lulu Le
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, Jiangxi, China.
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33
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Liu Y, Zhang Y, Chen C, Roy B, Li Q, Zhang W, Zhang X, Pu J, Li Y, Liu Y, Liao H, Wang J, Zhou R, Zhuo H, Li Y. lncRNA HIF1A-AS2 acts as an oncogene to regulate malignant phenotypes in cervical cancer. Front Oncol 2025; 15:1530677. [PMID: 40098697 PMCID: PMC11912943 DOI: 10.3389/fonc.2025.1530677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/06/2025] [Indexed: 03/19/2025] Open
Abstract
Background Long noncoding RNAs (lncRNAs) HIF1A-AS2 is upregulated in multiple human cancers and are associated with various aspects of tumor progression. However, the molecular mechanisms of HIF1A-AS2 in cervical cancer (CC) remain largely unknown. In this study, we aim to investigate the expression pattern and signaling pathways of HIF1A-AS2 in CC. Methods The study included a group of 20 CC patients, from whom tumor tissue specimens were collected. Additionally, three distinct CC cell lines (HeLa, SiHa, CaSki) were utilized. Quantitative real-time PCR (qRT-PCR) was used to assess the transcript levels of HIF1A-AS2 in these samples. Functional studies were performed by CCK-8, Transwell and Apoptosis assays. Databases including JASPAR, miRDB and Targetscan were used for the transcription factor or target miRNA prediction, subsequent dual luciferase activity assay, chromatin immunoprecipitation (ChIP) and Ago2 immunoprecipitation (RIP) were also adopted for validation. Results The study demonstrated that HIF1A-AS2 expression was elevated in clinical cervical cancer specimens and cultured cell lines in comparison to normal controls. Knockdown of HIF1A-AS2 notably inhibited the proliferation and invasion of cervical cancer cells, while inducing apoptosis. In contrast, HIF1A-AS2 overexpression promoted cellular proliferation and invasion and suppressed apoptosis. It was also identified that c-Jun functions as a transcription factor, activating HIF1A-AS2 expression. Additionally, HIF1A-AS2 was found to serve as a molecular sponge for miR-34b-5p, negatively regulating its expression. Furthermore, HIF1A-AS2 controlled the expression of radixin (RDX) by sponging the miR-34b-5p pathway. Conclusion Our findings indicate that c-Jun-activated HIF1A-AS2 acts as an oncogenic factor in CC by sponging miR-34b-5p to target radixin. These findings suggest that HIF1A-AS2 might be a viable and promising therapeutic target for cervical cancer treatment.
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Affiliation(s)
- Yang Liu
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
- Department of Clinical Laboratory, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China
| | - Yunyan Zhang
- Department of Pediatric Dentistry, Affiliated Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China
| | - Cha Chen
- Department of Clinical Laboratory, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Bhaskar Roy
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Qiantang District, Hangzhou, Zhejiang, China
| | - Qun Li
- Department of Clinical Laboratory, Guangzhou Liwan District People's Hospital, Guangzhou, Guangdong, China
| | - Wei Zhang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xuan Zhang
- Department of Clinical Laboratory, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Jieying Pu
- Department of Clinical Laboratory, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Yuguang Li
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Yanli Liu
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Huanlan Liao
- Department of Clinical Laboratory, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Jingjing Wang
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Rui Zhou
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Huiyan Zhuo
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
| | - Youqiang Li
- Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China
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Hu W, Du X, Wang X, Zhang K, Li J, Gao Y, An T, Zhang H, Zhang Y, Ren Z, Xu Y, Liu S. Explore autophagy-related lncRNA-miRNA-mRNA ceRNA networks for diagnosis of early-onset schizophrenia through transcriptome analysis. Front Psychiatry 2025; 16:1567148. [PMID: 40078531 PMCID: PMC11897231 DOI: 10.3389/fpsyt.2025.1567148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
Background The severe functional impairment and poor prognosis of early-onset schizophrenia (EOS) create a great need to identify effective biomarkers for early diagnosis in young psychiatric patients. Current research indicates a potential link between loss of autophagy function and emotional and behavioral abnormalities in individuals with psychiatric disorders. Materials and Methods This study aimed to explore diagnostic autophagy-related endogenous competitive RNA (ceRNA) networks for EOS patients. The messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) expression profiles were obtained from peripheral blood mononuclear cells of 18 EOS patients and 12 healthy controls (HC). A co-expression analysis was performed between 365 core lncRNAs and 55 differentially expressed autophagy-related genes (ARGs) to identify differentially expressed autophagy-related lncRNAs. Subsequently, five diagnostic autophagy-related lncRNAs were identified as candidate genes to construct a ceRNA regulatory network using least absolute shrinkage and selection operator (LASSO) Cox regression, and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive accuracy. Then, putative interactions among lncRNA-microRNAs (miRNAs)-mRNA were determined based on the lncRNASNP2 and TarBase databases. Results Three lncRNAs, twenty miRNAs, and ten mRNAs were selected to construct an autophagy-associated ceRNA network associated with EOS occurrence. Through protein-protein interaction network analysis, five hub mRNAs were identified, which exhibited good predictive ability in distinguishing EOS patients from healthy individuals. ROC curve analysis demonstrated that integrating three diagnostic lncRNAs (RP1-135L22.1, RP5-884C9.2, RP11-390F4.3) along with five hub mRNAs (EIF4G1, AKT1, BAX, WIPI2, MAPT) appeared to yield better diagnostic accuracy compared to using either lncRNAs or mRNAs alone. Furthermore, all three diagnostic lncRNAs and five hub mRNAs were positively correlated with at least two types of immune infiltration. Conclusion Through transcriptome analysis, we searched for diagnostic autophagy-related ceRNA networks, which provided valuable candidates for the early diagnosis of EOS.
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Affiliation(s)
- Wei Hu
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Basic Medical College, Shanxi Medical University, Taiyuan, China
| | - Xinzhe Du
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xinxia Wang
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Kexin Zhang
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Junxia Li
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yao Gao
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Ting An
- Shanxi Province Mental Health Center, Taiyuan Psychiatric Hospital, Taiyuan, China
| | - Hong Zhang
- Shanxi Province Mental Health Center, Taiyuan Psychiatric Hospital, Taiyuan, China
| | - Yu Zhang
- Basic Medical College, Shanxi Medical University, Taiyuan, China
| | - Zhiyong Ren
- Shanxi Province Mental Health Center, Taiyuan Psychiatric Hospital, Taiyuan, China
| | - Yong Xu
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
- The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Sha Liu
- Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China
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Lu Y, Huang Y, Zhu C, Li Z, Zhang B, Sheng H, Li H, Liu X, Xu Z, Wen Y, Zhang J, Zhang L. Cancer brain metastasis: molecular mechanisms and therapeutic strategies. MOLECULAR BIOMEDICINE 2025; 6:12. [PMID: 39998776 PMCID: PMC11861501 DOI: 10.1186/s43556-025-00251-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 01/06/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Brain metastases (BMs) are the most common intracranial tumors in adults and the major cause of cancer-related morbidity and mortality. The occurrence of BMs varies according to the type of primary tumors with most frequence in lung cancer, melanoma and breast cancer. Among of them, lung cancer has been reported to have a higher risk of BMs than other types of cancers with 40 ~ 50% of such patients will develop BMs during the course of disease. BMs lead to many neurological complications and result in a poor quality of life and short life span. Although the treatment strategies were improved for brain tumors in the past decades, the prognosis of BMs patients is grim. Poorly understanding of the molecular and cellular characteristics of BMs and the complicated interaction with brain microenvironment are the major reasons for the dismal prognosis of BM patients. Recent studies have enhanced understanding of the mechanisms of BMs. The newly identified potential therapeutic targets and the advanced therapeutic strategies have brought light for a better cure of BMs. In this review, we summarized the mechanisms of BMs during the metastatic course, the molecular and cellular landscapes of BMs, and the advances of novel drug delivery systems for overcoming the obstruction of blood-brain barrier (BBB). We further discussed the challenges of the emerging therapeutic strategies, such as synergistic approach of combining targeted therapy with immunotherapy, which will provide vital clues for realizing the precise and personalized medicine for BM patients in the future.
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Affiliation(s)
- Yu Lu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yunhang Huang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chenyan Zhu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhidan Li
- Center for Translational Medicine, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Bin Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hui Sheng
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Haotai Li
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xixi Liu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhongwen Xu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yi Wen
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jing Zhang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Liguo Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Ao S, Liang L, Peng L, Yang R, Chen Z, Deng T. Identification and validation of an m5C-related lncRNA signature for predicting prognosis and immune response in clear cell renal cell carcinoma. Discov Oncol 2025; 16:227. [PMID: 39987537 PMCID: PMC11847763 DOI: 10.1007/s12672-025-01987-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 02/17/2025] [Indexed: 02/25/2025] Open
Abstract
This study investigated whether m5C-related Long non-coding RNAs (lncRNAs) can predict clear cell renal cell carcinoma (ccRCC) patient prognosis. Co-expression and Cox regression analyses identified 9 prognostic lncRNAs, which were closely associated with tumor immune characteristics and immune escape. The model also predicted the sensitivity of drugs, including Entinostat, SB216763, and Sapitinib. In vitro experiments showed that GNG12-AS1 inhibited ccRCC cell proliferation and migration by reducing the activity of the ERK/GSK-3β/β-catenin pathway. Overall, these findings suggest that the 9 m5C-related lncRNAs can accurately predict ccRCC patient prognosis, providing potential applications for clinical and immunotherapy approaches. GNG12-AS1 emerges as a promising prognostic biomarker for predicting survival outcomes in ccRCC, potentially influencing cell migration through the activation of the ERK/GSK-3β/β-catenin signaling pathway.
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Affiliation(s)
- Shan Ao
- Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Leqi Liang
- Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Lei Peng
- Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Riwei Yang
- Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zugen Chen
- Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Tuo Deng
- Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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Wang S, Wang Q, Zheng J, Yan L, Pan Y, Jiang D, Li H, Liang S, He Z, Chen Q. Clinical implications and molecular mechanism of long noncoding RNA LINC00518 and protein-coding genes in skin cutaneous melanoma by genome‑wide investigation. Arch Dermatol Res 2025; 317:454. [PMID: 39987414 DOI: 10.1007/s00403-025-03961-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 12/26/2024] [Accepted: 02/03/2025] [Indexed: 02/24/2025]
Abstract
Skin cutaneous melanoma (SKCM) is a cancer with serious global impact. Long non-coding RNA was previously found to be associated with tumor prognosis. This research focuses on long intergenic non-protein coding (LINC) RNAs, and correlated protein-coding genes (PCGs), to explore their diagnostic and prognostic value, function and mechanism. Gene expression data was obtained from TCGA and Oncomine for analysis; in total there were 458 cases included in this study. LIN00518 and the 10 most highly correlated PCGs were selected to determine the diagnostic and prognostic value. We undertook bioinformatic analysis with LINC00518 and the prognostic-related PCGs in order to explore their molecular mechanism. The Connectivity Map was carried out for pharmacological target prediction and drug selection. Among the top 10 correlated PCGs, trafficking kinesin protein 2 (TRAK2), epilepsy of progressive myoclonus type 2 gene A (EPM2A) and melanocyte inducing transcription factor (MITF) had significant diagnostic value (all AUC > 0.7, P < 0.05). LINC00518, ras association domain family member 3 (RASSF3), cdk5 and Abl enzyme substrate 1 (CABLES1), kazrin, periplakin interacting protein (KAZN), EF-hand calcium binding domain 5 (EFCAB5) and MITF were significantly associated with prognosis (all adjusted P < 0.05). LINC00518 was associated with cell cycle process, melanogenesis, MAPK signaling pathway, cell division and DNA repair(all P < 0.05). Pharmacological targets analysis suggested results acquired eight potential target drugs. Up-regulation of LINC00518 is significantly associated with poor prognosis. TRAK2, EPM2A and MITF had diagnostic significance. RASSF3, CABLES1, KAZN, EFCAB5 and MITF had prognostic significance. This study provided novel biomarkers for SKCM.
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Affiliation(s)
- Shaoxi Wang
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Qiaoqi Wang
- The Emergency Department, The First Affiliated Hospital of Guangxi Medical University, No.6, Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Jiayu Zheng
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Lingxin Yan
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Yanqing Pan
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Diandian Jiang
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Huiling Li
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Siqiao Liang
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China
| | - Zhiyi He
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China.
| | - Quanfang Chen
- Department of Respiratory, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530000, People's Republic of China.
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Waliullah ASM, Qiu K, Dziegielewska B, Tran ML, Nguyen NN, Wang L, Pan A, Segovia N, Umarino S, Zhang J, Nguyen TM, Craig J, Tenen DG, Trinh BQ. An integrated DNA interactome and transcriptome profiling reveals a PU.1/enhancer RNA-mediated Feed-forward Regulatory Loop Regulating monocyte/macrophage development and innate immune functions. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.19.638695. [PMID: 40027734 PMCID: PMC11870581 DOI: 10.1101/2025.02.19.638695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
High expression of the myeloid master ETS transcription factor PU.1 drives the development of monocyte/macrophage (Mono/MΦ), a crucial cellular component of the innate immune system. Disruptions in normal expression patterns of PU.1 are linked to a variety myeloid malignancy and immune diseases. It is evidenced that PU.1 binds to and modulates enhancers of several myeloid genes. While noncoding RNAs transcribed from noncoding genes at the enhancers are increasingly reported to be involved in enhancer regulation, the crosstalk between PU.1 and noncoding RNAs in enhancer-mediated myeloid gene regulation in Mono/MΦ differentiation and immune response has not been systematically investigated. In this study, we interrogated the PU.1-mediated transcriptome and cistrome with our comprehensive collection of putative and verified enhancers. Among a repertoire of noncoding genes present at PU.1-bound enhancers, we discovered that PU.1 acts as a potent transcription factor inducer of the noncoding RNA LOUP , which we previously identified as an RNA inducer of PU.1. The genomic region within the LOUP locus occupied by PU.1 is characterized by the epigenetic features of a myeloid-specific super-enhancer. Targeted disruption of the PU.1-binding motifs resulted in the downregulation of LOUP promoter activity. Depletion of LOUP reduced the expression of Mono/MΦ cell markers as well as the transcriptional program associated with Mono/MΦ differentiation Mono/MΦ innate defense mechanisms, including phagocytosis, antimicrobial activity, and chemoattractant cytokine production. LOUP induces Mono/MΦ phagocytic activities. Collectively, our findings indicate that PU.1 and enhancer RNA LOUP are biomolecular components of an unidentified feed-forward loop that promotes their mutual expression, contributing to Mono/MΦ differentiation and innate immune functions. The identification of the PU.1/ LOUP regulatory circuit provides valuable insights into the mechanisms underlying cell-type and gene-specific enhancer activity and Mono/MΦ biology, as well as significant implications for advancing our understanding of immune diseases and myeloid malignancies.
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Meng J, Wang H, Liu Y, Wang Y, Li H. LNC159c Negatively Regulates Anthocyanin Biosynthesis via miR159c in Malus spectabilis Under Low Nitrogen. PLANT, CELL & ENVIRONMENT 2025. [PMID: 39969173 DOI: 10.1111/pce.15435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/10/2025] [Accepted: 02/07/2025] [Indexed: 02/20/2025]
Abstract
Low-nitrogen (LN) conditions typically promote anthocyanin biosynthesis in plants. Although previous studies primarily explored structural genes and transcription factors involved in anthocyanin biosynthesis, the role of long noncoding RNAs (lncRNAs) in this process under LN conditions remains less understood. This study identified LNC159c as a potential regulator of anthocyanin biosynthesis, with its expression notably downregulated under LN conditions. LNC159c functions as the host gene of miR159c, which regulates its expression. A dual-luciferase reporter assay and GFP signal detection demonstrated that miR159c inhibited MsMYB10 expression through base complementary pairing. Yeast one-hybrid (Y1H) and dual-LUC reporter assays jointly verified that MsMYB10 binds to the F3'H promoter. Stable overexpression in apple calli and transient overexpression in apple fruit peels and M. spectabilis leaves showed that LNC159c overexpression promoted miR159c expression, while inhibiting MsMYB10 expression and anthocyanin biosynthesis. MsMYB10 overexpression promoted anthocyanin biosynthesis, whereas the opposite results were observed in MsMYB10-silenced tissues. Thus, under LN conditions, reduced LNC159c expression limits miR159c production, relieving MsMYB10 inhibition and enhancing anthocyanin accumulation. These findings highlight the regulatory role of lncRNAs in anthocyanin biosynthesis under LN conditions.
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Affiliation(s)
- Jiaxin Meng
- Institute of Forestry and Pomology, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China
| | - Han Wang
- College of Landscape Architecture and Arts, Northwest A&F University, Yangling, China
| | - Yixin Liu
- College of Landscape Architecture and Arts, Northwest A&F University, Yangling, China
| | - Yu Wang
- College of Landscape Architecture and Arts, Northwest A&F University, Yangling, China
| | - Houhua Li
- College of Landscape Architecture and Arts, Northwest A&F University, Yangling, China
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40
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Kuznetsov NV, Statsenko Y, Ljubisavljevic M. An Update on Neuroaging on Earth and in Spaceflight. Int J Mol Sci 2025; 26:1738. [PMID: 40004201 PMCID: PMC11855577 DOI: 10.3390/ijms26041738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 02/06/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Over 400 articles on the pathophysiology of brain aging, neuroaging, and neurodegeneration were reviewed, with a focus on epigenetic mechanisms and numerous non-coding RNAs. In particular, this review the accent is on microRNAs, the discovery of whose pivotal role in gene regulation was recognized by the 2024 Nobel Prize in Physiology or Medicine. Aging is not a gradual process that can be easily modeled and described. Instead, multiple temporal processes occur during aging, and they can lead to mosaic changes that are not uniform in pace. The rate of change depends on a combination of external and internal factors and can be boosted in accelerated aging. The rate can decrease in decelerated aging due to individual structural and functional reserves created by cognitive, physical training, or pharmacological interventions. Neuroaging can be caused by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle, and environmental factors, which are especially noticeable in space environments where adaptive changes can trigger aging-like processes. Numerous candidate molecular biomarkers specific to neuroaging need to be validated to develop diagnostics and countermeasures.
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Affiliation(s)
- Nik V. Kuznetsov
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (Y.S.); (M.L.)
| | - Yauhen Statsenko
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (Y.S.); (M.L.)
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Milos Ljubisavljevic
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (Y.S.); (M.L.)
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
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Campo A, Aliquò F, Velletri T, Campo S. YRNAs: biosynthesis, structure, functions and involvment in cancer development. Discov Oncol 2025; 16:176. [PMID: 39945971 PMCID: PMC11825425 DOI: 10.1007/s12672-025-01957-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 02/07/2025] [Indexed: 02/16/2025] Open
Abstract
Y RNAs are a class of highly conserved small non-coding RNAs. Emerging evidences reported that Y RNAs and their Y RNA-derived small RNAs (YsRNAs) represent bioactive molecules and not simply structural RNAs involved in scaffolding and assembling. They can interact and regulate both localization and functions of several RNA-binding proteins implicated in a wide range of cellular processes such as DNA replication, RNA quality control and cellular stress responses. More evidences suggest functional involvement of Y RNAs in several type of disease such as cancer, immune related pathologies, neurological disorders and cardiovascular diseases. Nevertheless, there are many questions that still need to be answered for their functional and mechanistic understanding in a physiological and in a pathological context. In this review we will describe the current state of knowledge about YRNAs, their structure, biogenesis, functions and interaction with known proteins, as well their role in disease. The picture arising indicates their potential function as biomarkers for disease diagnosis, as well as therapeutical targets for building up tailored approaches in personalized medicine.
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Affiliation(s)
- Adele Campo
- Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Federica Aliquò
- Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Policlinico Universitario, via Consolare Valeria, 1, 98125, Messina, Italy
| | - Tania Velletri
- Department of Human Pathology of Adult and Childhood "Gaetano Barresi", University of Messina, Policlinico Universitario, via Consolare Valeria, 1, 98125, Messina, Italy.
| | - Salvatore Campo
- Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Policlinico Universitario, via Consolare Valeria, 1, 98125, Messina, Italy
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42
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Azam S, Sahu A, Pandey NK, Neupane M, Van Tassell CP, Rosen BD, Gandham RK, Rath SN, Majumdar SS. Advancing the Indian cattle pangenome: characterizing non-reference sequences in Bos indicus. J Anim Sci Biotechnol 2025; 16:21. [PMID: 39915889 PMCID: PMC11804092 DOI: 10.1186/s40104-024-01133-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/26/2024] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND India harbors the world's largest cattle population, encompassing over 50 distinct Bos indicus breeds. This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the genomic landscape of Indian cattle. To comprehensively characterize the genomic variation within Bos indicus and, specifically, dairy breeds, we aim to identify non-reference sequences and construct a comprehensive pangenome. RESULTS Five representative genomes of prominent dairy breeds, including Gir, Kankrej, Tharparkar, Sahiwal, and Red Sindhi, were sequenced using 10X Genomics 'linked-read' technology. Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb, comparable to the Bos indicus Brahman reference genome. A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods, revealing 8 Mb and 17.7 Mb of novel sequence respectively. A confident set of 6,844 Non-reference Unique Insertions (NUIs) spanning 7.57 Mb was identified through both methods, representing the pangenome of Indian Bos indicus breeds. Comparative analysis with previously published pangenomes unveiled 2.8 Mb (37%) commonality with the Chinese indicine pangenome and only 1% commonality with the Bos taurus pangenome. Among these, 2,312 NUIs encompassing ~ 2 Mb, were commonly found in 98 samples of the 5 breeds and designated as Bos indicus Common Insertions (BICIs) in the population. Furthermore, 926 BICIs were identified within 682 protein-coding genes, 54 long non-coding RNAs (lncRNA), and 18 pseudogenes. These protein-coding genes were enriched for functions such as chemical synaptic transmission, cell junction organization, cell-cell adhesion, and cell morphogenesis. The protein-coding genes were found in various prominent quantitative trait locus (QTL) regions, suggesting potential roles of BICIs in traits related to milk production, reproduction, exterior, health, meat, and carcass. Notably, 63.21% of the bases within the BICIs call set contained interspersed repeats, predominantly Long Interspersed Nuclear Elements (LINEs). Additionally, 70.28% of BICIs are shared with other domesticated and wild species, highlighting their evolutionary significance. CONCLUSIONS This is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India. The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.
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Affiliation(s)
- Sarwar Azam
- National Institute of Animal Biotechnology, Hyderabad, India
- Indian Institute of Technology Hyderabad, Sangareddy, India
| | - Abhisek Sahu
- National Institute of Animal Biotechnology, Hyderabad, India
| | | | - Mahesh Neupane
- Animal Genomics and Improvement Laboratory, USDA-ARS, Beltsville, MD, 20705, USA
| | - Curtis P Van Tassell
- Animal Genomics and Improvement Laboratory, USDA-ARS, Beltsville, MD, 20705, USA
| | - Benjamin D Rosen
- Animal Genomics and Improvement Laboratory, USDA-ARS, Beltsville, MD, 20705, USA.
| | - Ravi Kumar Gandham
- National Institute of Animal Biotechnology, Hyderabad, India.
- Animal Biotechnology, ICAR-NBAGR, Karnal, Haryana, India.
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Kulus M, Farzaneh M, Sheykhi-Sabzehpoush M, Ghaedrahmati F, Mehravar F, Józkowiak M, Piotrowska-Kempisty H, Bukowska D, Antosik P, Podhorska-Okołów M, Zabel M, Mozdziak P, Dzięgiel P, Kempisty B. Exosomes and non-coding RNAs: Exploring their roles in human myocardial dysfunction. Biomed Pharmacother 2025; 183:117853. [PMID: 39827809 DOI: 10.1016/j.biopha.2025.117853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 12/29/2024] [Accepted: 01/13/2025] [Indexed: 01/22/2025] Open
Abstract
Myocardial dysfunction, characterized by impaired cardiac muscle function, arises from diverse etiologies, including coronary artery disease, myocardial infarction, cardiomyopathies, hypertension, and valvular heart disease. Recent advancements have highlighted the roles of exosomes and non-coding RNAs in the pathophysiology of myocardial dysfunction. Exosomes are small extracellular vesicles released by cardiac and other cells that facilitate intercellular communication through their molecular cargo, including ncRNAs. ncRNAs are known to play critical roles in gene regulation through diverse mechanisms, impacting oxidative stress, fibrosis, and other factors associated with myocardial dysfunction. Dysregulation of these molecules correlates with disease progression, presenting opportunities for therapeutic interventions. This review explores the mechanistic interplay between exosomes and ncRNAs, underscoring their potential as biomarkers and therapeutic agents in myocardial dysfunction. Emerging evidence supports the use of engineered exosomes and modified ncRNAs to enhance cardiac repair by targeting signaling pathways associated with fibrosis, apoptosis, and angiogenesis. Despite promising preclinical results, delivery, stability, and immunogenicity challenges remain. Further research is needed to optimize clinical translation. Understanding these intricate mechanisms may drive the development of innovative strategies for diagnosing and treating myocardial dysfunction, ultimately improving patient outcomes.
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Affiliation(s)
- Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland
| | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Farhoodeh Ghaedrahmati
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Mehravar
- Department of Biostatistics and Epidemiology, School of Health, Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Małgorzata Józkowiak
- Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland; Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland
| | - Hanna Piotrowska-Kempisty
- Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland; Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun, Poland
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland
| | - Paweł Antosik
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland
| | - Marzenna Podhorska-Okołów
- Department of Human Morphology and Embryology, Division of Ultrastructure Research, Wroclaw Medical University, Wroclaw 50-368, Poland
| | - Maciej Zabel
- Division of Anatomy and Histology, University of Zielona Góra, Zielona Góra 65-046, Poland; Department of Human Morphology and Embryology, Division of Histology and Embryology, Wroclaw Medical University, Wroclaw 50-368, Poland
| | - Paul Mozdziak
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA; Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA
| | - Piotr Dzięgiel
- Department of Human Morphology and Embryology, Division of Histology and Embryology, Wroclaw Medical University, Wroclaw 50-368, Poland; Department of Physiotherapy, Wroclaw University School of Physical Education, Wroclaw, Poland
| | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland; Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland; Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA; Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czech Republic.
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Karaoglu B, Gur Dedeoglu B. A Regulatory Circuits Analysis Tool, "miRCuit," Helps Reveal Breast Cancer Pathways: Toward Systems Medicine in Oncology. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2025; 29:49-59. [PMID: 39853230 DOI: 10.1089/omi.2024.0201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2025]
Abstract
A systems medicine understanding of the regulatory molecular circuits that underpin breast cancer is essential for early cancer detection and precision/personalized medicine in clinical oncology. Transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) control gene expression and cell biology, and by extension, serve as pillars of the regulatory circuits that determine human health and disease. We report here the development of a regulatory circuit analysis program, miRCuit, constructing 10 different types of regulatory elements involving messenger RNA, miRNA, lncRNA, and TFs. Using the miRCuit, we analyzed expression profiling data from 179 invasive ductal breast carcinoma and 51 normal tissue samples from the Gene Expression Omnibus database. We identified eight circuit types along with two special types of circuits, one of which highlighted the significant roles of lncRNA CASC15, miR-130b-3p, and TF KLF5 in breast cancer development and progression. These findings advance our understanding of the regulatory molecules associated with breast cancer. Moreover, miRCuit offers a new avenue for users to construct circuits from regulatory molecules for potential applications to decipher disease pathogenesis.
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Affiliation(s)
- Begum Karaoglu
- Biotechnology Institute, Ankara University, Ankara, Turkey
- Intergen Genetics and Rare Diseases Diagnosis Center, Ankara, Turkey
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Han Y, Pu Q, Fan T, Wei T, Xu Y, Zhao L, Liu S. Long non-coding RNAs as promising targets for controlling disease vector mosquitoes. INSECT SCIENCE 2025; 32:24-41. [PMID: 38783627 DOI: 10.1111/1744-7917.13383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/10/2024] [Accepted: 04/16/2024] [Indexed: 05/25/2024]
Abstract
Hematophagous female mosquitoes are important vectors of numerous devastating human diseases, posing a major public health threat. Effective prevention and control of mosquito-borne diseases rely considerably on progress in understanding the molecular mechanisms of various life activities, and accordingly, the molecules that regulate the various life activities of mosquitoes are potential targets for implementing future vector control strategies. Many long non-coding RNAs (lncRNAs) have been identified in mosquitoes and significant progress has been made in determining their functions. Here, we present a comprehensive overview of the research advances on mosquito lncRNAs, including their molecular identification, function, and interaction with other non-coding RNAs, as well as their synergistic regulatory roles in mosquito life activities. We also highlight the potential roles of competitive endogenous RNAs in mosquito growth and development, as well as in insecticide resistance and virus-host interactions. Insights into the biological functions and mechanisms of lncRNAs in mosquito life activities, viral replication, pathogenesis, and transmission will contribute to the development of novel drugs and safe vaccines.
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Affiliation(s)
- Yujiao Han
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
| | - Qian Pu
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
| | - Ting Fan
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
| | - Tianqi Wei
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
| | - Yankun Xu
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
| | - Lu Zhao
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
| | - Shiping Liu
- State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400716, China
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Sethi SC, Singh R, Sahay O, Barik GK, Kalita B. Unveiling the hidden gem: A review of long non-coding RNA NBAT-1 as an emerging tumor suppressor and prognostic biomarker in cancer. Cell Signal 2025; 126:111525. [PMID: 39592019 DOI: 10.1016/j.cellsig.2024.111525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/09/2024] [Accepted: 11/20/2024] [Indexed: 11/28/2024]
Abstract
Previously considered junk or non-functional, long non-coding RNAs (lncRNAs) have emerged over the past few decades as pivotal components in both physiological and pathological processes, including cancer. Neuroblastoma-associated transcript-1 (NBAT-1) was initially discovered a decade ago as a risk-associated tumor suppressor lncRNA in neuroblastoma (NB). Subsequent studies have consistently demonstrated that NBAT-1 serves as a dedicated tumor suppressor in many cancers. NBAT-1 is significantly downregulated in cancer, which is closely linked to higher histological grades, increased metastasis, and poor survival in cancer patients suggesting NBAT-1's potential as a prognostic biomarker. In this review, we delve into the current body of literature, elucidating the tumor-suppressive roles of NBAT-1 and the underlying regulatory mechanisms in the context of human malignancies. Additionally, we shed light on the mechanisms contributing to the diminished expression of NBAT-1 and its potential as both a prognostic biomarker and a promising therapeutic target in cancer.
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Affiliation(s)
- Subhash Chandra Sethi
- Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Ragini Singh
- Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Osheen Sahay
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
| | - Ganesh Kumar Barik
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
| | - Bhargab Kalita
- Amrita Research Center, Amrita Vishwa Vidyapeetham, Amrita Hospital, Mata Amritanandamayi Marg, Faridabad 121002, India.
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Chen S, Liu M, Yi W, Li H, Yu Q. Micropeptides derived from long non-coding RNAs: Computational analysis and functional roles in breast cancer and other diseases. Gene 2025; 935:149019. [PMID: 39461573 DOI: 10.1016/j.gene.2024.149019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 10/29/2024]
Abstract
Long non-coding RNAs (lncRNAs), once thought to be mere transcriptional noise, are now revealing a hidden code. Recent advancements like ribosome sequencing have unveiled that many lncRNAs harbor small open reading frames and can potentially encode functional micropeptides. Emerging research suggests these micropeptides, not the lncRNAs themselves, play crucial roles in regulating homeostasis, inflammation, metabolism, and especially in breast cancer progression. This review delves into the rapidly evolving computational tools used to predict and validate lncRNA-encoded micropeptides. We then explore the diverse functions and mechanisms of action of these micropeptides in breast cancer pathogenesis, with a focus on their roles in various species. Ultimately, this review aims to illuminate the functional landscape of lncRNA-encoded micropeptides and their potential as therapeutic targets in cancer.
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Affiliation(s)
- Saisai Chen
- Department of Breast Surgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China
| | - Mengru Liu
- Department of Infection, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, China
| | - Weizhen Yi
- Department of Breast Surgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China
| | - Huagang Li
- Department of Breast Surgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China
| | - Qingsheng Yu
- Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei 230031, China.
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Wang Z, Zhen W, Wang Q, Sun Y, Jin S, Yu S, Wu X, Zhang W, Zhang Y, Xu F, Wang R, Xie Y, Sun W, Xu J, Zhang H. NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport. Stem Cell Res Ther 2025; 16:30. [PMID: 39876006 PMCID: PMC11776329 DOI: 10.1186/s13287-025-04156-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/21/2025] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging. METHODS BMSCs were isolated from alveolar bone of human volunteers aged 26-33 (young) and 66-78 (aged). NEAT1 expression and distribution changes during aging process were observed using fluorescence in situ hybridization (FISH) in young (3 months) and aged (18 months) mice or human BMSCs. Subsequent RNA pulldown and proteomic analyses, along with single-cell analysis, immunofluorescence, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP), were conducted to investigate that NEAT1 impairs the nuclear transport of mitotic FGF2 and contributes to BMSCs aging. RESULTS We reveal that NEAT1 undergoes significant upregulated and shifts from nucleus to cytoplasm in bone marrow and BMSCs during aging process. In which, the expression correlates with nuclear DNA content during karyokinesis, suggesting a link to mitogenic factor. Within NEAT1 knockdown, hallmarks of cellular aging, including senescence-associated secretory phenotype (SASP), p16, and p21, were significantly downregulated. RNA pulldown and proteomic analyses further identify NEAT1 involved in osteoblast differentiation, mitotic cell cycle, and ribosome biogenesis, highlighting its role in maintaining BMSCs differentiation and proliferation. Notably, as an essential growth factor of BMSCs, Fibroblast Growth Factor 2 (FGF2) directly abundant binds to NEAT1 and the sites enriched with nuclear localization motifs. Importantly, NEAT1 decreased the interaction between FGF2 and Karyopherin Subunit Beta 1 (KPNB1), influencing the nuclear transport of mitogenic FGF2. CONCLUSIONS Our findings position NEAT1 as a critical regulator of mitogenic protein networks that govern BMSC aging. Targeting NEAT1 might offer novel therapeutic strategies to rejuvenate aged BMSCs.
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Affiliation(s)
- Zifei Wang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Wenyu Zhen
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Qing Wang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Yuqiang Sun
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Siyu Jin
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Sensen Yu
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Xing Wu
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Wenhao Zhang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Yulong Zhang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Fei Xu
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Rui Wang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Yuxuan Xie
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China
| | - Wansu Sun
- Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
| | - Jianguang Xu
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.
| | - Hengguo Zhang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.
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Zeng Y, Zhu G, Peng W, Cai H, Lu C, Ye L, Jin M, Wang J. Transcriptome-Wide Analysis of N6-Methyladenosine-Modified Long Noncoding RNAs in Particulate Matter-Induced Lung Injury. TOXICS 2025; 13:98. [PMID: 39997913 PMCID: PMC11860755 DOI: 10.3390/toxics13020098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/24/2025] [Accepted: 01/25/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND N6-methyladenosine (m6A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m6A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) remains largely unexplored. METHODS Here, we establish a mouse model of PM-induced lung injury. We utilized m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) to identify differentially expressed m6A peaks on long non-coding RNAs (lncRNAs). Concurrently, we performed lncRNA sequencing (lncRNA-seq) to determine the differentially expressed lncRNAs. The candidate m6A-modified lncRNAs in the lung tissues of mice were identified through the intersection of the data obtained from these two sequencing approaches. RESULTS A total of 664 hypermethylated m6A peaks on 644 lncRNAs and 367 hypomethylated m6A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m6A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m6A-modified lncRNAs (lncRNA NR_003508, lncRNA uc008scb.1, and lncRNA ENSMUST00000159072) are identified through a joint analysis of the MeRIP-seq and lncRNA-seq data, and their validation is carried out using MeRIP-PCR and qRT-PCR. Analysis of the coding-non-coding gene co-expression network reveals that m6A-modified lncRNAs NR_003508 and uc008scb.1 participate in regulating pathways associated with inflammation and immune response. CONCLUSIONS This study first provides a comprehensive transcriptome-wide analysis of m6A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m6A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury.
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Affiliation(s)
- Yingying Zeng
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China; (Y.Z.); (G.Z.); (W.P.); (H.C.); (C.L.)
- Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
| | - Guiping Zhu
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China; (Y.Z.); (G.Z.); (W.P.); (H.C.); (C.L.)
- Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
| | - Wenjun Peng
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China; (Y.Z.); (G.Z.); (W.P.); (H.C.); (C.L.)
- Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
| | - Hui Cai
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China; (Y.Z.); (G.Z.); (W.P.); (H.C.); (C.L.)
| | - Chong Lu
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China; (Y.Z.); (G.Z.); (W.P.); (H.C.); (C.L.)
- Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
| | - Ling Ye
- Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
| | - Meiling Jin
- Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
| | - Jian Wang
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China; (Y.Z.); (G.Z.); (W.P.); (H.C.); (C.L.)
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Cai ZR, Zheng YQ, Hu Y, Ma MY, Wu YJ, Liu J, Yang LP, Zheng JB, Tian T, Hu PS, Liu ZX, Zhang L, Xu RH, Ju HQ. Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study. Gut 2025:gutjnl-2024-333522. [PMID: 39753334 DOI: 10.1136/gutjnl-2024-333522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/08/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND AND OBJECTIVE Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis. DESIGNS Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves. RESULTS RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effectively identify GC patients with negative gastrointestinal tumour biomarkers and those in early-stage. Furthermore, molecular biological assays revealed that knockdown of DGCR9 inhibited GC tumour growth. CONCLUSIONS Our proposed serum exosome ncRNA feature provides a promising liquid biopsy approach for enhancing the early diagnosis of GC.
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Affiliation(s)
- Ze-Rong Cai
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yong-Qiang Zheng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yan Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Meng-Yao Ma
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, People's Republic of China
| | - Yi-Jin Wu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Jia Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Lu-Ping Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Jia-Bo Zheng
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Tian Tian
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, People's Republic of China
| | - Pei-Shan Hu
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Ze-Xian Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Lin Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Rui-Hua Xu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Huai-Qiang Ju
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
- Department of Clinical Oncology, Shenzhen Key Laboratory for Cancer Metastasis and Personalized Therapy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China
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