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1
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Lu S, Cai J. Targeting therapy of PI3K/AKT signaling pathway via non-coding RNAs in diabetic retinopathy. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04093-z. [PMID: 40167630 DOI: 10.1007/s00210-025-04093-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 03/21/2025] [Indexed: 04/02/2025]
Abstract
Phosphoinositide 3-kinases (PI3Ks) are essential for maintaining glucose homeostasis. When these molecules malfunction, it can lead to increased blood glucose levels, which is the primary pathophysiological characteristic of diabetes. New data indicates that the PI3K/AKT signaling pathway is interacting reciprocally with non-coding RNAs (ncRNAs) such as miRNAs, long ncRNAs (lnc RNA), and circRNAs. Thus, it is clear that aberrant ncRNA regulation in the PI3K/AKT axis is connected to clinicopathological characteristics and is required for regulating biological processes. Diabetic retinopathy (DR) is a common complication of diabetes resulting from high blood sugar levels damaging the retina. Consequently, there is a greater need than ever for this prevention and treatment of disease. There has been a lot of interest in treating DR by targeting particular ncRNAs. The pathogenic functions of ncRNAs in DR are the main topic of this review. This review aims to explain the relationship between the PI3K/AKT signaling system and different miRNAs/lncRNAs/circRNAs and their significance in the biology of DR.
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Affiliation(s)
- Shuai Lu
- Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, 311201, China
| | - Jian Cai
- Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, 311201, China.
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2
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Pérez-Moreno P, Muñoz JP, Retamal MA. Molecular Interplay Between Non-Coding RNAs and Connexins and Its Possible Role in Cancer. Int J Mol Sci 2025; 26:2538. [PMID: 40141179 PMCID: PMC11942031 DOI: 10.3390/ijms26062538] [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: 02/07/2025] [Revised: 03/07/2025] [Accepted: 03/08/2025] [Indexed: 03/28/2025] Open
Abstract
Non-coding RNAs (ncRNAs) are sequences that do not encode for proteins and play key roles in different cellular processes, including cell proliferation and differentiation. On the other hand, connexins (Cxs) are transmembrane proteins that principally allow intercellular communication. In pathological conditions such as cancer, there is a deregulation in the expression and/or function of ncRNAs and Cxs, which in turn leads to an enhancement in the aggressive phenotype, such as a greater proliferative and invasive capacity. This suggests a plausible interplay between ncRNAs and Cxs. Based on that, this review aims to summarize the current knowledge regarding this relationship and to analyze how it may influence the development of aggressive traits in cancer cells and the clinicopathological features of cancer patients. Finally, we discuss the potential of ncRNAs and Cxs as promising clinical biomarkers for cancer diagnosis, prognosis, and therapeutic targeting.
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Affiliation(s)
- Pablo Pérez-Moreno
- Programa de Comunicación Celular en Cáncer, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7780272, Chile
| | - Juan P. Muñoz
- Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, Chile;
| | - Mauricio A. Retamal
- Programa de Comunicación Celular en Cáncer, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7780272, Chile
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3
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Quilles JC, Espada CR, Orsine LA, Defina TA, Almeida L, Holetz F, Cruz AK. A short ncRNA modulates gene expression and affects stress response and parasite differentiation in Leishmania braziliensis. Front Cell Infect Microbiol 2025; 15:1513908. [PMID: 39981380 PMCID: PMC11841412 DOI: 10.3389/fcimb.2025.1513908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 01/15/2025] [Indexed: 02/22/2025] Open
Abstract
The protozoan parasite Leishmania spp. is a causative agent of leishmaniasis, a disease that affects millions of people in more than 80 countries worldwide. Apart from its medical relevance, this organism has a genetic organization that is unique among eukaryotes. Studies of the mechanisms regulating gene expression in Leishmania led us to investigate noncoding RNAs (ncRNAs) as regulatory elements. We previously identified differentially expressed (DE) ncRNAs in Leishmania braziliensis with potential roles in the parasite biology and development. Herein, we present a functional analysis of one such DE ncRNA, the 147-nucleotide-long transcript ncRNA97, which is preferentially expressed in amastigotes, the replicative form within mammalian phagocytes. By RT-qPCR the ncRNA97 was detected in greater quantities in the nucleus under physiological conditions and in the cytoplasm under nutritional stress. Interestingly, the transcript is protected at the 5' end but is not processed by the canonical trypanosomatid trans-splicing mechanism, according to the RNA circularization assay. ncRNA97 knockout (KO) and addback (AB) transfectants were generated and subjected to phenotypic analysis, which revealed that the lack of ncRNA97 impairs the starvation response and differentiation to the infective form. Comparative transcriptomics of ncRNA97KO and parental cells revealed that transcripts encoding amastigote-specific proteins were affected. This pioneering work demonstrates that ncRNAs contribute to the developmental regulatory mechanisms of Leishmania.
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Affiliation(s)
- José C. Quilles
- Laboratory de Molecular Parasitology, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, FMRP/USP – University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Caroline R. Espada
- Laboratory de Molecular Parasitology, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, FMRP/USP – University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Lissur A. Orsine
- Laboratory de Molecular Parasitology, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, FMRP/USP – University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Tânia A. Defina
- Laboratory de Molecular Parasitology, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, FMRP/USP – University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Letícia Almeida
- Laboratory de Molecular Parasitology, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, FMRP/USP – University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Fabíola Holetz
- Laboratory of Gene Expression Regulation, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, PR, Brazil
| | - Angela K. Cruz
- Laboratory de Molecular Parasitology, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, FMRP/USP – University of São Paulo, Ribeirão Preto, SP, Brazil
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4
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Adjeroh DA, Zhou X, Paschoal AR, Dimitrova N, Derevyanchuk EG, Shkurat TP, Loeb JA, Martinez I, Lipovich L. Challenges in LncRNA Biology: Views and Opinions. Noncoding RNA 2024; 10:43. [PMID: 39195572 DOI: 10.3390/ncrna10040043] [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: 03/02/2024] [Revised: 06/26/2024] [Accepted: 07/04/2024] [Indexed: 08/29/2024] Open
Abstract
This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in the computational analysis of lncRNAs, lncRNAs and cancer, lncRNAs in sports, lncRNAs and COVID-19, and lncRNAs in human brain activity.
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Affiliation(s)
- Donald A Adjeroh
- Lane Department of Computer Science and Electrical Engineering, West Virginia University (WVU), Morgantown, WV 26506, USA
| | - Xiaobo Zhou
- Department of Bioinformatics and Systems Medicine, University of Texas Health Science Center, Houston, TX 77030, USA
| | - Alexandre Rossi Paschoal
- Department of Computer Science, Bioinformatics and Pattern Recognition Group, Federal University of Technology-Paraná-UTFPR, Curitiba 86300-000, Brazil
- Rosalind Franklin Institute, Harwell Science and Innovation Campus, Didcot OX11 0FA, UK
| | - Nadya Dimitrova
- Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
| | | | - Tatiana P Shkurat
- Department of Genetics, Southern Federal University, Rostov-on-Don 344090, Russia
| | - Jeffrey A Loeb
- Department of Neurology and Rehabilitation, The Center for Clinical and Translational Science, The University of Illinois NeuroRepository, University of Illinois, Chicago, IL 60607, USA
| | - Ivan Martinez
- Department of Microbiology, Immunology & Cell Biology, WVU Cancer Institute, West Virginia University (WVU) School of Medicine, Morgantown, WV 26505, USA
| | - Leonard Lipovich
- Shenzhen Huayuan Biological Science Research Institute, Shenzhen Huayuan Biotechnology Co., Ltd., Shenzhen 518000, China
- Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA
- College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou 325060, China
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5
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Chen C, Chen L, Liu X, Ma S, Chen K. Study on anti-BmNPV mechanism of branched-chain amino acid aminotransferases in silkworm. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2024; 156:105183. [PMID: 38636699 DOI: 10.1016/j.dci.2024.105183] [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: 02/07/2024] [Revised: 04/14/2024] [Accepted: 04/15/2024] [Indexed: 04/20/2024]
Abstract
Bombyx mori nucleopolyhedrovirus (BmNPV) is the most important virus that threatens sericulture industry. At present, there is no effective treatment for BmNPV infection in silkworms, and lncRNA plays an important role in biological immune response and host-virus interaction, but there are relatively few studies in silkworms. In this study, the four midgut tissue samples of the resistance strain NB (NB) and susceptible strain 306 (306) and the NB and 306 continuously infected with BmNPV for 96 h are used for whole transcriptome sequencing to analyze the differences in the genetic background of NB and 306 and the differences after inoculation of BmNPV, and the significantly different mRNA, miRNA and lnRNA between NB and 306 after BmNPV inoculation were screened. By comparing NB and 306, 2651 significantly different mRNAs, 57 significantly different miRNAs and 198 significantly different lncRNAs were screened. By comparing NB and 306 after BmNPV inoculation, 2684 significantly different mRNAs, 39 significantly different miRNAs and 125 significantly different lncRNAs were screened. According to the significantly different mRNA, miRNA and lncRNA screened from NB and 306 and NB and 306 after virus inoculation, the mRNA-miRNA-lncRNA regulatory network was constructed before and after virus inoculation, and the BmBCAT-Bomo_chr7_8305-MSTRG.3236.2 regulatory axis was screened from them, and it was found that BmBCAT was not Bomo_chr7_8305 regulated in the genetic background, after viral infection, MSTRG.3236.2 competes for binding Bomo_chr7_8305 regulates BmBCAT. The whole transcriptome sequencing results were verified by qPCR and the time-series expression analysis was performed to prove the reliability of the regulatory network. The BmBCAT-Bomo_chr7_8305-MSTRG.3236.2 regulatory axis may play a potential role in the interaction between silkworms and BmNPV. These results provide new insights into the interaction mechanism between silkworms and BmNPV.
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Affiliation(s)
- Can Chen
- School of Life Sciences, Jiangsu University, Zhenjiang, 212013, China
| | - Liang Chen
- School of Life Sciences, Jiangsu University, Zhenjiang, 212013, China
| | - Xiaoyong Liu
- School of Life Sciences, Jiangsu University, Zhenjiang, 212013, China
| | - Shangshang Ma
- School of Life Sciences, Jiangsu University, Zhenjiang, 212013, China
| | - Keping Chen
- School of Life Sciences, Jiangsu University, Zhenjiang, 212013, China.
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6
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Gan L, Zheng L, Zou J, Luo P, Chen T, Zou J, Li W, Chen Q, Cheng L, Zhang F, Qian B. Critical roles of lncRNA-mediated autophagy in urologic malignancies. Front Pharmacol 2024; 15:1405199. [PMID: 38939836 PMCID: PMC11208713 DOI: 10.3389/fphar.2024.1405199] [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: 03/22/2024] [Accepted: 05/23/2024] [Indexed: 06/29/2024] Open
Abstract
Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.
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Affiliation(s)
- Lifeng Gan
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Liying Zheng
- Department of Graduate, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Junrong Zou
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Peiyue Luo
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Tao Chen
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Jun Zou
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Wei Li
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Qi Chen
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Le Cheng
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Fangtao Zhang
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
| | - Biao Qian
- Department of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi, China
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7
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Xie X, Sinha S. Quantitative estimates of the regulatory influence of long non-coding RNAs on global gene expression variation using TCGA breast cancer transcriptomic data. PLoS Comput Biol 2024; 20:e1012103. [PMID: 38838009 PMCID: PMC11198904 DOI: 10.1371/journal.pcbi.1012103] [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: 01/19/2023] [Revised: 06/25/2024] [Accepted: 04/24/2024] [Indexed: 06/07/2024] Open
Abstract
Long non-coding RNAs (lncRNAs) have received attention in recent years for their regulatory roles in diverse biological contexts including cancer, yet large gaps remain in our understanding of their mechanisms and global maps of their targets. In this work, we investigated a basic unanswered question of lncRNA systems biology: to what extent can gene expression variation across individuals be attributed to lncRNA-driven regulation? To answer this, we analyzed RNA-seq data from a cohort of breast cancer patients, explaining each gene's expression variation using a small set of automatically selected lncRNA regulators. A key aspect of this analysis is that it accounts for confounding effects of transcription factors (TFs) as common regulators of a lncRNA-mRNA pair, to enrich the explained gene expression for lncRNA-mediated regulation. We found that for 16% of analyzed genes, lncRNAs can explain more than 20% of expression variation. We observed 25-50% of the putative regulator lncRNAs to be in 'cis' to, i.e., overlapping or located proximally to the target gene. This led us to quantify the global regulatory impact of such cis-located lncRNAs, which was found to be substantially greater than that of trans-located lncRNAs. Additionally, by including statistical interaction terms involving lncRNA-protein pairs as predictors in our regression models, we identified cases where a lncRNA's regulatory effect depends on the presence of a TF or RNA-binding protein. Finally, we created a high-confidence lncRNA-gene regulatory network whose edges are supported by co-expression as well as a plausible mechanism such as cis-action, protein scaffolding or competing endogenous RNAs. Our work is a first attempt to quantify the extent of gene expression control exerted globally by lncRNAs, especially those located proximally to their regulatory targets, in a specific biological (breast cancer) context. It also marks a first step towards systematic reconstruction of lncRNA regulatory networks, going beyond the current paradigm of co-expression networks, and motivates future analyses assessing the generalizability of our findings to additional biological contexts.
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Affiliation(s)
- Xiaoman Xie
- Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, Illinois, United States of America
| | - Saurabh Sinha
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, United States of America
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America
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8
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Zhang Y, Chen S, Tian Y, Fu X. Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects. Front Cell Infect Microbiol 2024; 14:1407261. [PMID: 38846354 PMCID: PMC11155306 DOI: 10.3389/fcimb.2024.1407261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/08/2024] [Indexed: 06/09/2024] Open
Abstract
SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.
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Affiliation(s)
| | | | - Yan Tian
- Department of Endocrinology and Metabolism, Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital and Cancer Center, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan, Chengdu, China
| | - Xianghui Fu
- Department of Endocrinology and Metabolism, Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital and Cancer Center, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan, Chengdu, China
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9
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Doghish AS, Radwan AF, Zaki MB, Elfar N, Moussa R, Walash Z, Alhamshry NAA, Mohammed OA, Abdel-Reheim MA, Elimam H. Decoding the role of long non-coding RNAs in gallbladder cancer pathogenesis: A review focus on signaling pathways interplay. Int J Biol Macromol 2024; 264:130426. [PMID: 38428766 DOI: 10.1016/j.ijbiomac.2024.130426] [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: 12/26/2023] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 03/03/2024]
Abstract
Gallbladder cancer (GBC) is one of the most aggressive types of biliary tree cancers and the commonest despite its rarity. It is infrequently diagnosed at an early stage, further contributing to its poor prognosis and low survival rate. The lethal nature of the disease has underlined a crucial need to discern the underlying mechanisms of GBC carcinogenesis which are still largely unknown. However, with the continual evolution in the research of cancer biology and molecular genetics, studies have found that non-coding RNAs (ncRNAs) play an active role in the molecular pathophysiology of GBC development. Dysregulated long non-coding RNAs (lncRNAs) and their interaction with intracellular signaling pathways contribute to malignancy and disease development. LncRNAs, a subclass of ncRNAs with over 200 nucleotides, regulate gene expression at transcriptional, translational, and post-translational levels and especially as epigenetic modulators. Thus, their expression abnormalities have been linked to malignancy and therapeutic resistance. lnsRNAs have also been found in GBC patients' serum and tumor tissue biopsies, highlighting their potential as novel biomarkers and for targeted therapy. This review will examine the growing involvement of lncRNAs in GBC pathophysiology, including related signaling pathways and their wider clinical use.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Abdullah F Radwan
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Nourhan Elfar
- School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital 11578, Cairo, Egypt; Egyptian Drug Authority (EDA), Ministry of Health and Population, Cairo 11567, Egypt
| | - Rewan Moussa
- Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Zahraa Walash
- Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Nora A A Alhamshry
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Mustafa Ahmed Abdel-Reheim
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef 62521, Egypt.
| | - Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt.
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10
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Lossi L, Castagna C, Merighi A. An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions. Int J Mol Sci 2024; 25:3881. [PMID: 38612690 PMCID: PMC11011998 DOI: 10.3390/ijms25073881] [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: 03/10/2024] [Revised: 03/27/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
Epigenetic changes are changes in gene expression that do not involve alterations to the DNA sequence. These changes lead to establishing a so-called epigenetic code that dictates which and when genes are activated, thus orchestrating gene regulation and playing a central role in development, health, and disease. The brain, being mostly formed by cells that do not undergo a renewal process throughout life, is highly prone to the risk of alterations leading to neuronal death and neurodegenerative disorders, mainly at a late age. Here, we review the main epigenetic modifications that have been described in the brain, with particular attention on those related to the onset of developmental anomalies or neurodegenerative conditions and/or occurring in old age. DNA methylation and several types of histone modifications (acetylation, methylation, phosphorylation, ubiquitination, sumoylation, lactylation, and crotonylation) are major players in these processes. They are directly or indirectly involved in the onset of neurodegeneration in Alzheimer's or Parkinson's disease. Therefore, this review briefly describes the roles of these epigenetic changes in the mechanisms of brain development, maturation, and aging and some of the most important factors dynamically regulating or contributing to these changes, such as oxidative stress, inflammation, and mitochondrial dysfunction.
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Affiliation(s)
| | | | - Adalberto Merighi
- Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Italy; (L.L.); (C.C.)
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11
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Ghahramani Almanghadim H, Karimi B, Poursalehi N, Sanavandi M, Atefi Pourfardin S, Ghaedi K. The biological role of lncRNAs in the acute lymphocytic leukemia: An updated review. Gene 2024; 898:148074. [PMID: 38104953 DOI: 10.1016/j.gene.2023.148074] [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: 10/10/2023] [Revised: 11/29/2023] [Accepted: 12/08/2023] [Indexed: 12/19/2023]
Abstract
The cause of leukemia, a common malignancy of the hematological system, is unknown. The structure of long non-coding RNAs (lncRNAs) is similar to mRNA but no ability to encode proteins. Numerous malignancies, including different forms of leukemia, are linked to Lnc-RNAs. It is verified that the carcinogenesis and growth of a variety of human malignancies are significantly influenced by aberrant lncRNA expression. The body of evidence linking various types of lncRNAs to the etiology of leukemia has dramatically increased during the past ten years. Some lncRNAs are therefore anticipated to function as novel therapeutic targets, diagnostic biomarkers, and clinical outcome predictions. Additionally, these lncRNAs may provide new therapeutic options and insight into the pathophysiology of diseases, particularly leukemia. Thus, this review outlines the present comprehension of leukemia-associated lncRNAs.
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Affiliation(s)
| | - Bahareh Karimi
- Department of Cellular and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Negareh Poursalehi
- Department of Medical Biotechnology, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | | | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Ave., Azadi Sq., 81746-73441 Isfahan, Iran.
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12
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Shi J, Wang Z, Wang Z, Shao G, Li X. Epigenetic regulation in adult neural stem cells. Front Cell Dev Biol 2024; 12:1331074. [PMID: 38357000 PMCID: PMC10864612 DOI: 10.3389/fcell.2024.1331074] [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: 10/31/2023] [Accepted: 01/12/2024] [Indexed: 02/16/2024] Open
Abstract
Neural stem cells (NSCs) exhibit self-renewing and multipotential properties. Adult NSCs are located in two neurogenic regions of adult brain: the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Maintenance and differentiation of adult NSCs are regulated by both intrinsic and extrinsic signals that may be integrated through expression of some key factors in the adult NSCs. A number of transcription factors have been shown to play essential roles in transcriptional regulation of NSC cell fate transitions in the adult brain. Epigenetic regulators have also emerged as key players in regulation of NSCs, neural progenitor cells and their differentiated progeny via epigenetic modifications including DNA methylation, histone modifications, chromatin remodeling and RNA-mediated transcriptional regulation. This minireview is primarily focused on epigenetic regulations of adult NSCs during adult neurogenesis, in conjunction with transcriptional regulation in these processes.
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Affiliation(s)
- Jiajia Shi
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
| | - Zilin Wang
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
| | - Zhijun Wang
- Zhenhai Lianhua Hospital, Ningbo City, Zhejiang, China
| | - Guofeng Shao
- Department of Cardiothoracic Surgery, Lihuili Hospital Affiliated to Ningbo University, Ningbo City, Zhejiang, China
| | - Xiajun Li
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
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13
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Cheng J, Tao J, Li B, Shi Y, Liu H. The lncRNA HCG4 regulates the RIG-I-mediated IFN production to suppress H1N1 swine influenza virus replication. Front Microbiol 2024; 14:1324218. [PMID: 38274760 PMCID: PMC10808666 DOI: 10.3389/fmicb.2023.1324218] [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: 10/19/2023] [Accepted: 12/27/2023] [Indexed: 01/27/2024] Open
Abstract
Influenza A virus (IAV) non-structural protein 1 (NS1) is a virulence factor that allows the virus to replicate efficiently by suppressing host innate immune responses. Previously, we demonstrated that the serine (S) at position 42 of NS1 in H1N1 swine influenza virus (SIV) is a critical residue in interferon (IFN) resistance, thus facilitating viral infections. Here, by lncRNA-seq, a total of 153 differentially expressed lncRNAs were identified, and the lncRNA HCG4 was selected due to its significantly higher expression after infection with the NS1 S42P mutant virus. Overexpression of HCG4 enhanced IFN-β production and suppressed SIV infection, highlighting the potential antiviral activity of HCG4 against SIV. Further investigation suggested that HCG4 served as a positive feedback mediator for RIG-I signaling. It alleviated the inhibitory effect on RIG-I K63-linked ubiquitination by NS1 protein, thereby resulting in an increase in RIG-I-mediated IFN production. Taken together, our findings demonstrate that HCG4 modulates the innate immune response to SIV infection through K63-linked RIG-I ubiquitination, providing insights into the role of lncRNAs in controlling viral infections.
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Affiliation(s)
- Jinghua Cheng
- Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, Shanghai, China
- Shanghai Key Laboratory of Agricultural Genetic Breeding, Shanghai, China
- Shanghai Engineering Research Center of Pig Breeding, Shanghai, China
| | - Jie Tao
- Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, Shanghai, China
- Shanghai Key Laboratory of Agricultural Genetic Breeding, Shanghai, China
- Shanghai Engineering Research Center of Pig Breeding, Shanghai, China
| | - Benqiang Li
- Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, Shanghai, China
- Shanghai Key Laboratory of Agricultural Genetic Breeding, Shanghai, China
- Shanghai Engineering Research Center of Pig Breeding, Shanghai, China
| | - Ying Shi
- Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, Shanghai, China
- Shanghai Key Laboratory of Agricultural Genetic Breeding, Shanghai, China
- Shanghai Engineering Research Center of Pig Breeding, Shanghai, China
| | - Huili Liu
- Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, Shanghai, China
- Shanghai Key Laboratory of Agricultural Genetic Breeding, Shanghai, China
- Shanghai Engineering Research Center of Pig Breeding, Shanghai, China
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Wang Y, Fu Y, Lu Y, Chen S, Zhang J, Liu B, Yuan Y. Unravelling the complexity of lncRNAs in autophagy to improve potential cancer therapy. Biochim Biophys Acta Rev Cancer 2023; 1878:188932. [PMID: 37329993 DOI: 10.1016/j.bbcan.2023.188932] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/30/2023] [Accepted: 06/10/2023] [Indexed: 06/19/2023]
Abstract
Autophagy is well-known as an internal catabolic process that is evolutionarily conserved and performs the key biological function in maintaining cellular homeostasis. It is tightly controlled by several autophagy-related (ATG) proteins, which are closely associated with many types of human cancers. However, what has remained controversial is the janus roles of autophagy in cancer progression. Interestingly, the biological function of long non-coding RNAs (lncRNAs) in autophagy has been gradually understood in different types of human cancers. More recently, numerous studies have demonstrated that several lncRNAs may regulate some ATG proteins and autophagy-related signaling pathways to either activate or inhibit the autophagic process in cancer. Thus, in this review, we summarize the latest advance in the knowledge of the complicated relationships between lncRNAs and autophagy in cancer. Also, the in-depth dissection of the lncRNAs-autophagy-cancers axis involved in this review would shed new light on discovery of more potential cancer biomarkers and therapeutic targets in the future.
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Affiliation(s)
- Yi Wang
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yuqi Fu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yingying Lu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Siwei Chen
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jin Zhang
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
| | - Bo Liu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Yong Yuan
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
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15
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Lin H, Qu L, Chen G, Zhang C, Lu L, Chen Y. Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma. Eur J Med Res 2023; 28:236. [PMID: 37452355 PMCID: PMC10347828 DOI: 10.1186/s40001-023-01194-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 06/25/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND Necroptosis has been reported to play a critical role in occurrence and progression of cancer. The dysregulation of long non-coding RNAs (lncRNAs) is associated with the progression and metastasis of clear cell renal cell carcinoma (CCRCC). However, research on necroptosis-related lncRNAs in the tumor heterogeneity and prognosis of CCRCC is not completely unclear. This study aimed to analysis the tumor heterogeneity among CCRCC subgroups and construct a CCRCC prognostic signature based on necroptosis-related lncRNAs. METHODS Weighted gene co-expression network analysis (WGCNA) was performed to identify necroptosis-related lncRNAs. A preliminary classification of molecular subgroups was performed by non-negative matrix factorization (NMF) consensus clustering analysis. Comprehensive analyses, including fraction genome altered (FGA), tumor mutational burden (TMB), DNA methylation alterations, copy number variations (CNVs), and single nucleotide polymorphisms (SNPs), were performed to explore the potential factors for tumor heterogeneity among the three subgroups. Subsequently, we constructed a predictive signature by multivariate Cox regression. Nomogram, calibration curves, decision curve analysis (DCA), and time-dependent receiver-operating characteristics (ROC) were used to validate and evaluate the signature. Finally, immune correlation analyses, including immune-related signaling pathways, immune cell infiltration status and immune checkpoint gene expression level, were also performed. RESULTS Seven necroptosis-related lncRNAs were screened out by WGCNA, and three subgroups were classified by NMF consensus clustering analysis. There were significant differences in survival prognosis, clinicopathological characteristics, enrichments of immune-related signaling pathway, degree of immune cell infiltration, and expression of immune checkpoint genes in the various subgroups. Most importantly, we found that 26 differentially expressed genes (DEGs) among the 3 subgroups were not affected by DNA methylation alterations, CNVs and SNPs. On the contrary, these DEGs were associated with the seven necroptosis-related lncRNAs. Subsequently, the identified RP11-133F8.2 and RP11-283G6.4 by multivariate Cox regression analysis were involved in the risk model, which could serve as an independent prognostic factor for CCRCC. Finally, qRT-PCR confirmed the differential expression of the two lncRNAs. CONCLUSIONS These findings contributed to understanding the function of necroptosis-related lncRNAs in CCRCC and provided new insights of prognostic evaluation and optimal therapeutic strategy for CCRCC.
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Affiliation(s)
- Hang Lin
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, China
| | - Lingzhi Qu
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, China
| | - Guanqiu Chen
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Chunfang Zhang
- Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Liqing Lu
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, China
- Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Yongheng Chen
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, China
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Huang X, Yu J, Lai S, Li Z, Qu F, Fu X, Li Q, Zhong X, Zhang D, Li H. Long Non-Coding RNA LINC00052 Targets miR-548p/Notch2/Pyk2 to Modulate Tumor Budding and Metastasis of Human Breast Cancer. Biochem Genet 2023; 61:336-353. [PMID: 35918619 DOI: 10.1007/s10528-022-10255-y] [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: 01/09/2022] [Accepted: 06/22/2022] [Indexed: 01/24/2023]
Abstract
Abnormal expression of long non-coding RNAs (lncRNAs) is involved in many pathological processes of cancers. However, the role of lncRNA LINC00052 in breast cancer progression is still unclear. Here, LINC00052 expression was detected by in situ hybridization and quantitative real-time PCR assays. Cell Counting Kit-8, wound healing, and transwell assays were used to investigate changes in the proliferation, migration, and invasion of breast cancer cells. MiR-548p was found associated with LINC00052 or Notch2 by RNA pull-down, dual-luciferase reporter, and qRT-PCR assays. The effect of LINC00052 on lung metastasis was explored through in vivo experiments. High LINC00052 expression was observed in breast cancer tissues and cells. LINC00052 silencing inhibited the proliferation, migration, and invasion of MCF7 cells, and LINC00052 overexpression produced the opposite results. MiR-548p, a target gene of LINC00052, partially rescued the effects of LINC00052 on proliferation, migration, and invasion of MCF7. Notch2 was the target of miR-548p and LINC00052 could promote Notch2 expression. Moreover, the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2), a downstream factor of Notch2, was increased by LINC00052, and a Pyk2 mutant could inhibit the cell migration and invasion induced by LINC00052 overexpression in MDA-MB-468 cells, which was similar to the function of the miR-548p mimic. We further demonstrated that LINC00052 exacerbated the metastases of breast cancer cells in vivo. Our research demonstrated that LINC00052 is highly expressed in breast cancer and promotes breast cancer proliferation, migration, and invasion via the miR-548p/Notch2/Pyk2 axis. LINC00052 could serve as a potential therapeutic target for breast cancer.
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Affiliation(s)
- Xiaojia Huang
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Junli Yu
- Department of Medical Ultrasound, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, Guangdong, China
| | - Shengqing Lai
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Zongyan Li
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Fanli Qu
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Xiaoyan Fu
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Qian Li
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Xiaofang Zhong
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China
| | - Dawei Zhang
- Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, Guangdong, China
| | - Haiyan Li
- Department of Breast Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong, China.
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Yu M, Xue S, Chen X, Wu K, Ju L, Tang J, Xiong A, Chen X, Ying X. Long Non-coding RNA UCA1a Promotes Proliferation via PKM2 in Cervical Cancer. Reprod Sci 2023; 30:601-614. [PMID: 35927414 DOI: 10.1007/s43032-022-01042-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 07/12/2022] [Indexed: 01/17/2023]
Abstract
Cervical cancer is a common malignancy that affects women worldwide. The long non-coding RNA (lncRNA) urothelial cancer-associated 1a (UCA1a) is reported to be significantly upregulated in cervical cancer. However, the exact role of UCA1a in cervical cancer remains unknown. This study aimed to identify two core promoter regions in UCA1a, which are essential for CEBPA-dependent transcription and FOXL1-, FOXL4-, and FOXL6-dependent activation, respectively. RNA sequencing results showed that overexpression of UCA1a resulted in extensive changes in the gene expression profile of HeLa cells, especially in the signaling pathway that regulates tumorgenesis. Mass spectrometry assay was conducted to show that pyruvate kinase M2 (PKM2) was a UCA1a-interacting protein. The 400 ~ 800 nt long region of UCA1a at the 5' end and the A1B domain of PKM2 were critical for the UCA1a-PKM2 interaction. Functional assays were performed to show that PKM2 was sufficient and necessary for UCA1a-induced proliferation of HeLa cells, which was partly due to the regulating of nuclear translocation and stabilization of PKM2. These findings provide a novel mechanism for UCA1a to regulate Hela cells by ubiquitination degradation of PKM2 and suggest that UCA1a may play a key role in the progression of cervical cancer.
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Affiliation(s)
- Minmin Yu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China. .,Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China.
| | - Songlin Xue
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Xin Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Kaihua Wu
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Lili Ju
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Juan Tang
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Aiwei Xiong
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China
| | - Xiaoxiang Chen
- Department of Gynecologic Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research &, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
| | - Xiaoyan Ying
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China.
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Asadi M, Gholampour MA, Kompani F, Alizadeh S. Expression of Long Non-Coding RNA H19 in Acute Lymphoblastic Leukemia. CELL JOURNAL 2023; 25:1-10. [PMID: 36680478 PMCID: PMC9868437 DOI: 10.22074/cellj.2022.8315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Indexed: 01/22/2023]
Abstract
OObjective: Long non-coding RNA (lncRNA) H19 has essential roles in growth, migration, invasion, and metastasis of most cancers. H19 dysregulation is present in a large number of solid tumors and leukemia. However, the expression level of H19 in acute lymphoblastic leukemia (ALL) has not been elucidated yet. The current study aimed to explore H19 expression in ALL patients and cell lines. MATERIALS AND METHODS This experimental study was conducted in bone marrow (BM) samples collected from 25 patients with newly diagnosed ALL. In addition, we cultured the RPMI-8402, Jurkat, Ramos, and Daudi cell lines and assessed the effects of internal (hypoxia) and external (chemotherapy medications L-asparaginase [ASP] and vincristine [VCR]) factors on h19 expression. The expressions of H19, P53, c-Myc, HIF-1α and β-actin were performed using quantitative real-time polymerase chain reaction (qRT-PCR) method. RESULTS There was significantly increased H19 expression in the B-cell ALL (B-ALL, P<0.05), T-cell ALL (T-ALL, P<0.01) patients and the cell lines. This upregulation was governed by the P53, HIF-1α, and c-Myc transcription factors. We observed that increased c-Myc expression induced H19 expression; however, P53 adversely affected H19 expression. In addition, the results indicated that chemotherapy changed the gene expression pattern. There was a considerable decrease in H19 expression after exposure to chemotherapy medications; nonetheless, hypoxia induced H19 expression through P53 downregulation. CONCLUSION Our findings suggest that H19 may have an important role in pathogenesis in ALL and may act as a promising and potential therapeutic target.
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Affiliation(s)
- Marjan Asadi
- Hematology Department, School of Allied Medicine, Tehran University of Medical Science, Tehran, Iran,P.O.Box: 1417935840Hematology DepartmentSchool of Allied MedicineTehran University of Medical
ScienceTehranIran
| | - Mohammad Ali Gholampour
- Hematology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Farzad Kompani
- Division of Hematology and Oncology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical
Science, Tehran, Iran
| | - Shaban Alizadeh
- Hematology Department, School of Allied Medicine, Tehran University of Medical Science, Tehran, Iran
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Sarkar S, Chowdhury SG, Karmakar P. Drugging non-coding RNAs-A new light of hope in senescence-related cancer therapy. Chem Biol Drug Des 2022; 101:1216-1228. [PMID: 36573649 DOI: 10.1111/cbdd.14200] [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: 09/29/2022] [Revised: 12/13/2022] [Accepted: 12/17/2022] [Indexed: 12/28/2022]
Abstract
Cancer is the most prevalent disease of concern worldwide for several decades. Diverse therapeutic aspects are in applications to control this phenomenal disease and also for decennaries. Among many causes and consequences of cancer, senescence has gained much interest in recent times. Senescence, also termed aging, is the natural process that induces cancer in neighboring cells through Senescence-Associated-Secretory Phenotypes (SASPs) production. As a cure or preventive measure of cancer progression, studies already light upon multiple proteins and their roles in associated pathways but the aspect of different non-coding RNAs (ncRNAs) is emerging recently and is under extensive research. Different approaches toward controlling senescence and inhibiting senescent cell accumulation are other aspects of cancer procurement. Thus, the role of ncRNA molecules in senescence and aging is getting much more interest as an alternate therapy for cancer treatment. In this review, at first, the roles of different ncRNAs related to several cellular processes are described. Then we tried to highlight the roles of different non-coding RNAs in senescence-induced cancer formation that extends with increasing age and emphasized non-coding RNAs as a therapeutic target solely or in combination with small molecules where drugging of small molecules targeting these non-coding RNAs can control cancer development.
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Affiliation(s)
- Swarupa Sarkar
- Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India
| | | | - Parimal Karmakar
- Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India
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20
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RNA-Mediated Regulation of Meiosis in Budding Yeast. Noncoding RNA 2022; 8:ncrna8060077. [PMID: 36412912 PMCID: PMC9680404 DOI: 10.3390/ncrna8060077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/30/2022] [Accepted: 08/31/2022] [Indexed: 11/17/2022] Open
Abstract
Cells change their physiological state in response to environmental cues. In the absence of nutrients, unicellular fungi such as budding yeast exit mitotic proliferation and enter the meiotic cycle, leading to the production of haploid cells that are encased within spore walls. These cell state transitions are orchestrated in a developmentally coordinated manner. Execution of the meiotic cell cycle program in budding yeast, Saccharomyces cerevisiae, is regulated by the key transcription factor, Ime1. Recent developments have uncovered the role of non-coding RNA in the regulation of Ime1 and meiosis. In this review, we summarize the role of ncRNA-mediated and RNA homeostasis-based processes in the regulation of meiosis in Saccharomyces cerevisiae.
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A novel lncRNA MTAR1 promotes cancer development through IGF2BPs mediated post-transcriptional regulation of c-MYC. Oncogene 2022; 41:4736-4753. [DOI: 10.1038/s41388-022-02464-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 08/24/2022] [Accepted: 08/31/2022] [Indexed: 11/09/2022]
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22
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Zhang X, Sun B, Bai Y, Canário AVM, Xu X, Li J. Long non-coding RNAs are involved in immune resistance to Aeromonas hydrophila in black carp (Mylopharyngodon piceus). FISH & SHELLFISH IMMUNOLOGY 2022; 127:366-374. [PMID: 35772677 DOI: 10.1016/j.fsi.2022.06.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 05/24/2022] [Accepted: 06/19/2022] [Indexed: 06/15/2023]
Abstract
A growing number of studies identified long non-coding RNAs (lncRNAs) to be closely associated with immune function through the regulation of immune cell differentiation and immune cell effector function. Here we tested whether lncRNAs are involved in immune function in black carp (Mylopharyngodon piceus) through the exposure to Aeromonas hydrophila and analysis of the spleen gene expression response using RNA-seq. A total of 9036 lncRNAs were identified with high confidence. Differential expression analysis identified a total of 3558 DElncRNAs (Differential expression lncRNA) involved in A. hydrophila infection and 4526 target genes corresponding to DElncRNAs. After screening 4526 target genes in the InnateDB database, a total of 150 immunity genes were identified. After GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis of the obtained immunity genes, the Toll-like receptor (TLR) signaling pathway, TLR2, TLR3, TLR5, and TLR8 were identified as particularly significant in A. hydrophyla-resistant black carp. At the same time, the Ras signaling pathway was particularly enriched in the spleen of susceptible black carp. Analysis of PPI (protein-protein interaction) networks of the obtained immune genes identified SRC (SRC Proto-Oncogene), MYD88 (Myeloid differentiation primary response 88), MAPK3 (Mitogen-Activated Protein Kinase 3), MYC (MYC Proto-Oncogene) as main hub genes regulated by lncRNA and possibly mediating a mechanism of susceptibility to bacteria. These results establish a functional role of lncRNAs and a mechanistic base for the immune response in black carp resistant to A. hydrophila.
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Affiliation(s)
- Xueshu Zhang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; CCMAR/CIMAR Centre of Marine Sciences, University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal
| | - Bingyan Sun
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China
| | - Yulin Bai
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Adelino V M Canário
- International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; CCMAR/CIMAR Centre of Marine Sciences, University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
| | - Xiaoyan Xu
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, Shanghai, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China.
| | - Jiale Li
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, Shanghai, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China.
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Wang C, Yang Q, Han Y, Liu H, Wang Y, Huang Y, Zheng Y, Li W. A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment. Stem Cell Res Ther 2022; 13:229. [PMID: 35659362 PMCID: PMC9166574 DOI: 10.1186/s13287-022-02897-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 12/11/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND A series of biochemical responses, including hypoxia and aseptic inflammation, occur in periodontal ligament cells (PDLCs) during periodontal tissue remodeling of orthodontic tooth movement (OTM). However, the role of long non-coding RNA (lncRNA) in these responses is still largely unknown. We investigated the role of the lncRNA SNHG8 in hypoxic and inflammatory responses during OTM and explored the underlying mechanisms. METHODS The expression pattern of SNHG8, and hypoxic and inflammatory responses under compressive force were analyzed by qRT-PCR, immunohistochemistry, and western blotting, in vivo and in vitro. The effect of overexpression or knockdown of SNHG8 on the nuclear factor-kappaB (NF-κB) pathway was evaluated. RNA sequencing was performed for mechanistic analysis. The interaction between SNHG8 and hypoxia-inducible factor (HIF)-1α was studied using catRAPID, RNA immunoprecipitation, and RNA pulldown assays. The effect of the SNHG8-HIF-1α interaction on the NF-κB pathway was determined by western blotting. RESULTS The NF-κB pathway was activated, and HIF-1α release was stabilized, in PDLCs under compressive force as well as in OTM model rats. The SNHG8 level markedly decreased both in vivo and in vitro. Overexpression of SNHG8 decreased the expression levels of inflammatory cytokines, the phosphorylation of p65, and the degradation of IκBα in PDLCs, whereas knockdown of SNHG8 reversed these effects. Mechanically, RNA sequencing showed that differentially expressed genes were enriched in cellular response to hypoxia after SNHG8 overexpression. SNHG8 binds to HIF-1α, thus preventing HIF-1 from activating downstream genes, including those related to the NF-κB pathway. CONCLUSION SNHG8 binds to HIF-1α. During OTM, the expression of SNHG8 dramatically decreased, releasing free functional HIF-1α and activating the downstream NF-κB pathway. These data suggest a novel lncRNA-regulated mechanism during periodontal tissue remodeling in OTM.
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Affiliation(s)
- Chenxin Wang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Qiaolin Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yineng Han
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Hao Liu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yue Wang
- Department of Stomatology, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China
| | - Yiping Huang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
| | - Weiran Li
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
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Wu W, Zhong W, Xu Q, Yan J. Silencing of long non-coding RNA ZFAS1 alleviates LPS-induced acute lung injury by mediating the miR-96-5p/OXSR1 axis in sepsis. Am J Med Sci 2022; 364:66-75. [DOI: 10.1016/j.amjms.2022.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 10/20/2021] [Accepted: 03/30/2022] [Indexed: 11/01/2022]
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Xuan P, Gong Z, Cui H, Li B, Zhang T. Fully connected autoencoder and convolutional neural network with attention-based method for inferring disease-related lncRNAs. Brief Bioinform 2022; 23:6561435. [PMID: 35362511 DOI: 10.1093/bib/bbac089] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/17/2022] [Accepted: 02/23/2022] [Indexed: 11/14/2022] Open
Abstract
Since abnormal expression of long noncoding RNAs (lncRNAs) is often closely related to various human diseases, identification of disease-associated lncRNAs is helpful for exploring the complex pathogenesis. Most of recent methods concentrate on exploiting multiple kinds of data related to lncRNAs and diseases for predicting candidate disease-related lncRNAs. These methods, however, failed to deeply integrate the topology information from the meta-paths that are composed of lncRNA, disease and microRNA (miRNA) nodes. We proposed a new method based on fully connected autoencoders and convolutional neural networks, called ACLDA, for inferring potential disease-related lncRNA candidates. A heterogeneous graph that consists of lncRNA, disease and miRNA nodes were firstly constructed to integrate similarities, associations and interactions among them. Fully connected autoencoder-based module was established to extract the low-dimensional features of lncRNA, disease and miRNA nodes in the heterogeneous graph. We designed the attention mechanisms at the node feature level and at the meta-path level to learn more informative features and meta-paths. A module based on convolutional neural networks was constructed to encode the local topologies of lncRNA and disease nodes from multiple meta-path perspectives. The comprehensive experimental results demonstrated ACLDA achieves superior performance than several state-of-the-art prediction methods. Case studies on breast, lung and colon cancers demonstrated that ACLDA is able to discover the potential disease-related lncRNAs.
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Affiliation(s)
- Ping Xuan
- School of Computer Science and Technology, Heilongjiang University, Harbin 150080, China
| | - Zhe Gong
- School of Computer Science and Technology, Heilongjiang University, Harbin 150080, China
| | - Hui Cui
- Department of Computer Science and Information Technology, La Trobe University, Melbourne 3083, Australia
| | - Bochong Li
- Center for Frontier Medical Engineering, Chiba University, Chiba 2638522, Japan
| | - Tiangang Zhang
- School of Mathematical Science, Heilongjiang University, Harbin 150080, China
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Zhang G, Liu SL, Yi WT, Dong YP, Wan YX. Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2. Kaohsiung J Med Sci 2022; 38:530-541. [PMID: 35258173 DOI: 10.1002/kjm2.12527] [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: 09/15/2021] [Revised: 02/05/2022] [Accepted: 02/17/2022] [Indexed: 11/07/2022] Open
Abstract
Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.
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Affiliation(s)
- Gang Zhang
- Department of Urology section, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Song-Lin Liu
- Department of Urology section, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Wen-Ting Yi
- Department of Medical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Yu-Ping Dong
- Department of Hematopathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
| | - Yin-Xu Wan
- Department of Urology section, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
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Wang B, Wang M, Jia S, Li T, Yang M, Ge F. Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells. J Proteome Res 2022; 21:1137-1152. [DOI: 10.1021/acs.jproteome.2c00009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Bing Wang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Min Wang
- The Analysis and Testing Center, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Shuzhao Jia
- The Analysis and Testing Center, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Tao Li
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Mingkun Yang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Feng Ge
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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Zhan T, Zhu K, Hu J, Ma X, Zhu Y, Zhang C. LncRNA ODRUL regulates progression of osteosarcoma by regulating IL-6 via sponging miR-6874-3p. Exp Cell Res 2022; 412:113050. [PMID: 35114192 DOI: 10.1016/j.yexcr.2022.113050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 01/23/2022] [Accepted: 01/28/2022] [Indexed: 12/22/2022]
Abstract
Accumulating evidence has shown that many long non-coding RNAs (lncRNA) participate in the tumorigenesis, including osteosarcoma (OS). Of them, lncRNA ODRUL was previously reported to act as a possible oncogene in OS doxorubicin resistance. However, the underlying molecular mechanism of ODRUL involved in the progression of OS still remains to be thoroughly investigated. In the current study, we reported another mechanism by which ODRUL regulates OS progression. QRT-PCR and WB were conducted to detect ODRUL, miR-6874-3p and IL-6 expression in OS tissues and cells. The Kaplan-Meier was used to assess the relevance between the expression level of miR-6874-3p and the overall survival of OS patients. Wound healing assays and Transwell assays were used to evaluate the invasion and migration of OS cells. Furthermore, the binding sites of ODRUL and IL-6 to miR-6874-3p were predicted by bioinformatics and verified by dual-luciferase reporter gene assays. ODRUL and IL-6 were highly expressed in OS cells and tissues, while miR-6874-3p was expressed at low levels. The overall survival of high miR-6874-3p expression of OS patients was longer than that of low miR-6874-3p expression of OS patients. MiR-6874-3p overexpression markedly inhibited the progression of OS cells. Both ODRUL and IL-6 could bind to miR-6874-3p at the predicted binding sites which were authenticated by dual-luciferase reporter gene assay. MiR-6874-3p could inhibit OS cell proliferation and metastasis and ODRUL could reverse the suppression induced by miR-6874-3p in vivo. In conclusion, ODRUL could effectively sponge miR-6874-3p to upregulate the expression of IL-6 in OS progression.
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Affiliation(s)
- Taicheng Zhan
- Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China
| | - Kunpeng Zhu
- Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China
| | - Jianping Hu
- Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China
| | - Xiaolong Ma
- Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China
| | - Yurun Zhu
- Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China
| | - Chunlin Zhang
- Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China.
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Chen J, Zheng Q, Liu F, Jin H, Wu X, Xi Y. LINC00152 acts as a competing endogenous RNA of HMGA1 to promote the growth of gastric cancer cells. J Clin Lab Anal 2022; 36:e24192. [PMID: 35014092 PMCID: PMC8841176 DOI: 10.1002/jcla.24192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 11/25/2021] [Accepted: 12/08/2021] [Indexed: 12/24/2022] Open
Abstract
Background Long noncoding RNAs (lncRNAs) play important roles in almost every stage of cancer development. Given the competing endogenous RNA (ceRNA) hypothesis for the regulation of gene expression, we investigated the role of LINC00152 as a ceRNA in gastric cancer (GC) cells. Methods Gastric cancer cell lines were used in this study. Mimics of miRNAs and siRNA were used to evaluate the interaction between LINC00152 and HMGA1. The quantitative real‐time polymerase chain reaction was performed for analyzing gene expression at the transcriptional level. Flow cytometry assay of cell cycle and western blot analysis of related protein expression levels were performed. Online databases such as TCGA and TIMER were used to determine the possibility of HMGA1 and LINC00152 as GC markers and their role in immune infiltration. Results Treating GC cell lines with LINC00152 siRNAs downregulated the expression of HMGA1. The cell cycle was arrested in the S phase following a reduction in LINC00152 or HMGA1 expression, whereas the expression of the cell cycle inhibitor P27 increased. In this study, we showed that acting as a ceRNA of HMGA1, LINC00152 has the same function as HMGA1, considering that it could control the cell cycle and promote GC cell proliferation. The TCGA database showed that LINC00152 might be used as a diagnostic marker for GC. Conclusions These findings provide mechanistic insights into the role of LINC00152 as a ceRNA to regulate HMGA1 expression in GC cells, where it can promote the proliferation of the GC cells by regulating the expression of the P27.
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Affiliation(s)
- Jiayi Chen
- Department of Experimental Pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo, China.,Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Qingfang Zheng
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Fang Liu
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China.,Ningbo Haishu District Center for Disease Control and Prevention, Ningbo, China
| | - Han Jin
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Xiaoyue Wu
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
| | - Yang Xi
- Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, China
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30
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Ma F, Li CC, Zhang CY. Nucleic acid amplification-integrated single-molecule fluorescence imaging for in vitro and in vivo biosensing. Chem Commun (Camb) 2021; 57:13415-13428. [PMID: 34796887 DOI: 10.1039/d1cc04799j] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Single-molecule fluorescence imaging is among the most advanced analytical technologies and has been widely adopted for biosensing due to its distinct advantages of simplicity, rapidity, high sensitivity, low sample consumption, and visualization capability. Recently, a variety of nucleic acid amplification approaches have been developed to provide a straightforward and highly efficient way for amplifying low abundance target signals. The integration of single-molecule fluorescence imaging with nucleic acid amplification has greatly facilitated the construction of various fluorescent biosensors for in vitro and in vivo detection of DNAs, RNAs, enzymes, and live cells with high sensitivity and good selectivity. Herein, we review the advances in the development of fluorescent biosensors by integrating single-molecule fluorescence imaging with nucleic acid amplification based on enzyme (e.g., DNA polymerase, RNA polymerase, exonuclease, and endonuclease)-assisted and enzyme-free (e.g., catalytic hairpin assembly, entropy-driven DNA amplification, ligation chain reaction, and hybridization chain reaction) strategies, and summarize the principles, features, and in vitro and in vivo applications of the emerging biosensors. Moreover, we discuss the remaining challenges and future directions in this area. This review may inspire the development of new signal-amplified single-molecule biosensors and promote their practical applications in fundamental and clinical research.
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Affiliation(s)
- Fei Ma
- Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China. .,School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
| | - Chen-Chen Li
- Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China. .,Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Shandong Key Laboratory of Biochemical Analysis, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
| | - Chun-Yang Zhang
- Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China.
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Shang F, Ding BY, Zhang YT, Wu JJ, Pan ST, Wang JJ. Genome-wide analysis of long non-coding RNAs and their association with wing development in Aphis citricidus (Hemiptera: Aphididae). INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY 2021; 139:103666. [PMID: 34619323 DOI: 10.1016/j.ibmb.2021.103666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 09/28/2021] [Accepted: 09/28/2021] [Indexed: 06/13/2023]
Abstract
Long non-coding RNAs (lncRNAs) play critical roles in the various physiological processes of insects. The wing is a successful adaptation allowing insects to escape from unfavorable environments, while information on lncRNAs related to wing development is limited. In this study, we constructed 12 libraries from two RNA-seq comparisons: 4th instar winged nymphs versus winged adults and 4th instar wingless nymphs versus wingless adults in the brown citrus aphid Aphis citricidus, to identify the wing development-associated lncRNAs. A total of 2914 lncRNAs were identified and 50 lncRNAs were differentially expressed during the 4th instar winged nymphs to winged adults transition, and 28 lncRNAs changed during the 4th instar wingless nymphs to wingless adults transition. The differentially expressed lncRNAs were grouped into six clusters according to the expression patterns in the combined two-winged morphs. lncRNA Ac_lnc54106.1 was up-regulated during 4th instar winged nymphs to winged adults transition, but a lack of change during the 4th instar wingless nymphs to wingless adults transition implied a critical role in the specific regulation of wing development. RNA interference of Ac_lnc54106.1 resulted in malformed wings. Targets prediction, expression patterns, and RNAi assay results showed that Ac_lnc54106.1 may target the PiggyBac transposable element-derived protein 4 (PGBD4) gene, decrease expression of the canonical wing development-related genes, and finally regulate wing development. The systematic identification of lncRNAs in an aphid increases our understanding of how non-coding RNA mediates the wing plasticity of insects.
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Affiliation(s)
- Feng Shang
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400716, China; State Cultivation Base of Crop Stress Biology for Southern Mountainous Land, Academy of Agricultural Sciences, Southwest University, Chongqing, China.
| | - Bi-Yue Ding
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400716, China; State Cultivation Base of Crop Stress Biology for Southern Mountainous Land, Academy of Agricultural Sciences, Southwest University, Chongqing, China.
| | - Yong-Te Zhang
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400716, China.
| | - Jin-Jin Wu
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400716, China.
| | - Si-Tong Pan
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400716, China.
| | - Jin-Jun Wang
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, 400716, China; State Cultivation Base of Crop Stress Biology for Southern Mountainous Land, Academy of Agricultural Sciences, Southwest University, Chongqing, China.
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Sun X, Chen Z. Cancer-associated fibroblast-derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression. Oncol Lett 2021; 22:696. [PMID: 34457051 PMCID: PMC8358620 DOI: 10.3892/ol.2021.12957] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/28/2021] [Indexed: 12/20/2022] Open
Abstract
Aberrant C-C motif chemokine ligand 5 (CCL5) is associated with disease progression, poor prognosis and chemotherapy resistance in human malignancy. The tumor microenvironment (TME) contributes to chemotherapy resistance. However, the role of cancer-associated fibroblasts (CAFs)-derived CCL5 is not well documented. Hence, the present study aimed to investigate the effects of CAFs on chemotherapy resistance in A549 non-small cell lung cancer (NSCLC) cells and the underlying mechanism. Primary CAFs isolated from patients with NSCLC were found to express and secrete elevated levels of CCL5, which attenuated cisplatin (DDP)-induced apoptosis, as indicated by flow cytometry analysis. In addition, CCL5 upregulated the expression levels of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in the tumor cells, and silencing HOTAIR in tumor cells enhanced the cytotoxic effect of cisplatin, characterized by decreased cell viability and increased apoptotic rate. Mechanistically, HOTAIR was found to inactivate the caspase-3/BCL-2 signaling pathway in A549 NSCLC cells. Collectively, the current study demonstrated that CAFs in the TME may serve a crucial role in the higher expression levels of CCL5 in tumors and that CAF-derived CCL5 may promote cisplatin resistance via upregulating lncRNA HOTAIR expression.
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Affiliation(s)
- Xiangjun Sun
- Department of Respiratory and Critical Care Medicine, Hanchuan People's Hospital, Hanchuan, Hubei 431600, P.R. China
| | - Zhijie Chen
- Department of General Surgery, Hanchuan People's Hospital, Hanchuan, Hubei 431600, P.R. China
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Zhu Z, Zhang X, Jiang Y, Ruan S, Huang F, Zeng H, Liu M, Xia W, Zeng F, Chen J, Cui Y, Chen H. NEAT1 functions as a key mediator of BMP2 to promote osteogenic differentiation of renal interstitial fibroblasts. Epigenomics 2021; 13:1171-1186. [PMID: 34325517 DOI: 10.2217/epi-2021-0212] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Aim: To clarify the mechanism of NEAT1, an aberrantly upregulated lncRNA in Randall's plaques (RP) similar to biomineralization, in mediating osteogenic differentiation of human renal interstitial fibroblasts. Materials & methods: A comprehensive strategy of bioinformatic analysis and experimental verification was performed. Results: BMP2 silence abolished the osteogenic differentiation of human renal interstitial fibroblasts promoted by NEAT1. Mechanically, NEAT1 not only induced the nucleolar translocation of EGR1 binding to BMP2 promotor, but also functioned as a sponge of miR-129-5p in the cytoplasm to promote BMP2 expression. Moreover, there was a positive correlation between NEAT1 and BMP2 expression in RP instead of normal renal papilla. Conclusion: NEAT1 acted as a key mediator of BMP2 to promote human renal interstitial fibroblast osteogenic differentiation, through which NEAT1 might be involved in RP formation.
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Affiliation(s)
- Zewu Zhu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Xiaoqiong Zhang
- Transplantation Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yingcheng Jiang
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Shuhao Ruan
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Fang Huang
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Huimin Zeng
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Minghui Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Weiping Xia
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Feng Zeng
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yu Cui
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Hequn Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
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Wang P, Zhang H, Zhao W, Dai N. Silencing of long non-coding RNA KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in childhood pneumonia. BMC Pulm Med 2021; 21:247. [PMID: 34301223 PMCID: PMC8299180 DOI: 10.1186/s12890-021-01609-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 07/13/2021] [Indexed: 01/02/2023] Open
Abstract
Purpose Long non-coding RNAs (lncRNAs) play important roles in the development of pneumonia. We aimed to explore the role of the lncRNA KCNQ1OT1 in pneumonia and its underlying mechanisms. Methods The expression of KCNQ1OT1, FOXM1, and miR-370-3p was detected in the serum of 24 children with pneumonia and in 24 healthy controls. Normal human embryonic lung-derived diploid fibroblasts (WI-38 cells) were stimulated with LPS (10 μg/mL) to simulate the cellular model of pneumonia, and cell viability, apoptosis, and inflammation were analysed. Dual luciferase reporter and/or RNA binding protein immunoprecipitation assays were performed to test the relationship between miR-370-3p and KCNQ1OT1/FOXM1. Mice were intratracheally administered LPS (5 mg/kg) to induce an in vivo model of pneumonia, and pathological injury and inflammation were analysed. Results The expression of KCNQ1OT1 and FOXM1 was up-regulated, and miR-370-3p was down-regulated in the serum of children with pneumonia, LPS-treated WI-38 cells, and in lung tissues of LPS-treated mice. Silencing of KCNQ1OT1 or overexpression of miR-370-3p suppressed cell apoptosis and inflammation and facilitated cell viability in LPS-treated WI-38 cells. KCNQ1OT1 directly targets miR-370-3p and negatively regulates its expression. FOXM1 was targeted by miR-370-3p and negatively modulated by miR-370-3p. In addition, silencing of KCNQ1OT1 mitigated LPS-induced lung injury and inflammation in mice. The protective effects of KCNQ1OT1 silencing in LPS-treated WI-38 cells and mice were reversed by silencing of miR-370-3p or overexpression of FOXM1. Conclusion Silencing of KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in pneumonia. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-021-01609-0.
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Affiliation(s)
- Ping Wang
- Department of Pediatrics I, The People's Hospital of Shouguang, No. 43, Jiankang Street, Shouguang City, 262700, Shandong Province, China
| | - Haitao Zhang
- Department of Pediatrics I, The People's Hospital of Shouguang, No. 43, Jiankang Street, Shouguang City, 262700, Shandong Province, China
| | - Weiqing Zhao
- Department of Digestive Internal Medicine, Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), No. 4, Renmin Road, Shibei District, Qingdao City, 266033, Shandong Province, China
| | - Nini Dai
- Department of Pediatrics I, Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), No. 4, Renmin Road, Shibei District, Qingdao City, 266033, Shandong Province, China.
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Wang P, Yang S, Dai S, Ni Q, Liu H, Yu L, Lu K, Han G, Huang J. Expression and Clinical Value of LncRNA GAPLINC in Esophageal Squamous Cell Carcinoma. Onco Targets Ther 2021; 14:4039-4045. [PMID: 34262290 PMCID: PMC8274232 DOI: 10.2147/ott.s299394] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 06/14/2021] [Indexed: 12/24/2022] Open
Abstract
Background The long noncoding RNA (lncRNA) GAPLINC, or gastric adenocarcinoma predictive long intergenic ncRNA, plays a carcinogenic role in a variety of different tumor types. There is limited information regarding the biological function of GAPLINC in the development of esophageal squamous cell carcinoma (ESCC). Methods Surgical tissue samples of 40 patients undergoing ESCC radical surgery were collected, including ESCC tissues and corresponding adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA GAPLINC in the human ESCC cell line (TE11). The function role of LncRNA GAPLINC was detected after specific siRNA interference and overexpression in the TE11 cell line. The effects of LncRNA GAPLINC on ESCC cell proliferation, migration and invasion abilities were investigated by flow cytometry, using the Cell Counting Kit-8 (CCK-8), and by Transwell migration assays, respectively. Results The expression of lncRNA GAPLINC in ESCC tissues was significantly higher than that in corresponding adjacent normal tissues (P<0.05) and correlated with the degree of tumor differentiation (P<0.05). Compared with human esophageal normal epithelial cell lines, the expression of LncRNA GAPLINC was significantly higher in the human ESCC cell line (P<0.05). CCK-8 assays showed that LncRNA GAPLINC overexpression increased the growth rate of cells (P<0.05). Transwell experiments showed that LncRNA GAPLINC overexpression increased the ability of cell migration and invasion compared to control cells (P<0.05). Annexin V assay revealed that LncRNA GAPLINC silencing increased early stage apoptosis (P<0. 05). Conclusion Our results suggest that LncRNA GAPLINC may be used as a biomarker for the diagnosis and monitoring of ESCC, and may play an oncogenic role in ESCC.
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Affiliation(s)
- Peng Wang
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Song Yang
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Shengbin Dai
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Qingtao Ni
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Huilan Liu
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Lei Yu
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Kaijin Lu
- Department of Thoracic Surgery, The Fifth Affiliated Hospital of Nantong University, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu, 225300, People's Republic of China
| | - Gaohua Han
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
| | - Junxing Huang
- Department of Oncology, The Fifth Affiliated Hospital of Nantong University (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, 225300, People's Republic of China
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Di Fiore R, Suleiman S, Felix A, O’Toole SA, O’Leary JJ, Ward MP, Beirne J, Sabol M, Ozretić P, Yordanov A, Vasileva-Slaveva M, Kostov S, Nikolova M, Said-Huntingford I, Ayers D, Ellul B, Pentimalli F, Giordano A, Calleja-Agius J. An Overview of the Role of Long Non-Coding RNAs in Human Choriocarcinoma. Int J Mol Sci 2021; 22:ijms22126506. [PMID: 34204445 PMCID: PMC8235025 DOI: 10.3390/ijms22126506] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/11/2021] [Accepted: 06/15/2021] [Indexed: 02/08/2023] Open
Abstract
Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.
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Affiliation(s)
- Riccardo Di Fiore
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
- Correspondence: (R.D.F.); (J.C.-A.); Tel.: +356-2340-3871 (R.D.F.); +356-2340-1892 (J.C.-A.)
| | - Sherif Suleiman
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
| | - Ana Felix
- Department of Pathology, Campo dos Mártires da Pátria, Instituto Portugues de Oncologia de Lisboa, NOVA Medical School, UNL, 130, 1169-056 Lisboa, Portugal;
| | - Sharon A. O’Toole
- Departments of Obstetrics and Gynaecology and Histopathology, Trinity St James’s Cancer Institute, Trinity College Dublin, 8 Dublin, Ireland;
| | - John J. O’Leary
- Department of Histopathology, Trinity College Dublin, Trinity St James’s Cancer Institute, 8 Dublin, Ireland; (J.J.O.); (M.P.W.)
| | - Mark P. Ward
- Department of Histopathology, Trinity College Dublin, Trinity St James’s Cancer Institute, 8 Dublin, Ireland; (J.J.O.); (M.P.W.)
| | - James Beirne
- Department of Gynaecological Oncology, Trinity St James Cancer Institute, St James Hospital, 8 Dublin, Ireland;
| | - Maja Sabol
- Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.S.); (P.O.)
| | - Petar Ozretić
- Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.S.); (P.O.)
| | - Angel Yordanov
- Department of Gynecologic Oncology, Medical University Pleven, 5800 Pleven, Bulgaria;
| | | | - Stoyan Kostov
- Department of Gynecology, Medical University Varna “Prof. Dr. Paraskev Stoyanov”, 9002 Varna, Bulgaria;
| | - Margarita Nikolova
- Saint Marina University Hospital—Pleven, Medical University Pleven, 5800 Pleven, Bulgaria;
| | - Ian Said-Huntingford
- Department of Histopathology, Mater Dei Hospital, Birkirkara Bypass, MSD 2090 Msida, Malta;
| | - Duncan Ayers
- Centre for Molecular Medicine & Biobanking, University of Malta, MSD 2080 Msida, Malta; (D.A.); (B.E.)
- Faculty of Biology, Medicine and Human Sciences, The University of Manchester, Manchester M1 7DN, UK
| | - Bridget Ellul
- Centre for Molecular Medicine & Biobanking, University of Malta, MSD 2080 Msida, Malta; (D.A.); (B.E.)
| | - Francesca Pentimalli
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy;
| | - Antonio Giordano
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Jean Calleja-Agius
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
- Correspondence: (R.D.F.); (J.C.-A.); Tel.: +356-2340-3871 (R.D.F.); +356-2340-1892 (J.C.-A.)
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He X, Kuang G, Zuo Y, Li S, Zhou S, Ou C. The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress. Front Med (Lausanne) 2021; 8:626423. [PMID: 33959621 PMCID: PMC8093385 DOI: 10.3389/fmed.2021.626423] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 03/25/2021] [Indexed: 12/14/2022] Open
Abstract
Diabetic nephropathy (DN) is one of the main complications of diabetes and the main cause of diabetic end-stage renal disease, which is often fatal. DN is usually characterized by progressive renal interstitial fibrosis, which is closely related to the excessive accumulation of extracellular matrix and oxidative stress. Non-coding RNAs (ncRNAs) are RNA molecules expressed in eukaryotic cells that are not translated into proteins. They are widely involved in the regulation of biological processes, such as, chromatin remodeling, transcription, post-transcriptional modification, and signal transduction. Recent studies have shown that ncRNAs play an important role in the occurrence and development of DN and participate in the regulation of oxidative stress in DN. This review clarifies the functions and mechanisms of ncRNAs in DN-related oxidative stress, providing valuable insights into the prevention, early diagnosis, and molecular therapeutic targets of DN.
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Affiliation(s)
- Xiaoyun He
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Gaoyan Kuang
- Department of Orthopedics, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yi Zuo
- Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Shuangxi Li
- Department of Pathophysiology, Hunan University of Medicine, Huaihua, China
| | - Suxian Zhou
- Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Chen Y, Zitello E, Guo R, Deng Y. The function of LncRNAs and their role in the prediction, diagnosis, and prognosis of lung cancer. Clin Transl Med 2021; 11:e367. [PMID: 33931980 PMCID: PMC8021541 DOI: 10.1002/ctm2.367] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/22/2021] [Accepted: 03/05/2021] [Indexed: 12/24/2022] Open
Abstract
Lung cancer remains a major threat to human health. Low dose CT scan (LDCT) has become the main method of early screening for lung cancer due to the low sensitivity of chest X-ray. However, LDCT not only has a high false positive rate, but also entails risks of overdiagnosis and cumulative radiation exposure. In addition, cumulative radiation by LDCT screening and subsequent follow-up can increase the risk of lung cancer. Many studies have shown that long noncoding RNAs (lncRNAs) remain stable in blood, and profiling of blood has the advantages of being noninvasive, readily accessible and inexpensive. Serum or plasma assay of lncRNAs in blood can be used as a novel detection method to assist LDCT while improving the accuracy of early lung cancer screening. LncRNAs can participate in the regulation of various biological processes. A large number of researches have reported that lncRNAs are key regulators involved in the progression of human cancers through multiple action models. Especially, some lncRNAs can affect various hallmarks of lung cancer. In addition to their diagnostic value, lncRNAs also possess promising potential in other clinical applications toward lung cancer. LncRNAs can be used as predictive markers for chemosensitivity, radiosensitivity, and sensitivity to epidermal growth factor receptor (EGFR)-targeted therapy, and as well markers of prognosis. Different lncRNAs have been implicated to regulate chemosensitivity, radiosensitivity, and sensitivity to EGFR-targeted therapy through diverse mechanisms. Although many challenges need to be addressed in the future, lncRNAs have bright prospects as an adjunct to radiographic methods in the clinical management of lung cancer.
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Affiliation(s)
- Yu Chen
- Department of Quantitative Health SciencesJohn A. Burns School of Medicine, University of Hawaii at ManoaHonoluluHawaiiUSA
- Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human ResourcesUniversity of Hawaii at ManoaHonoluluHawaiiUSA
| | - Emory Zitello
- Department of Quantitative Health SciencesJohn A. Burns School of Medicine, University of Hawaii at ManoaHonoluluHawaiiUSA
- Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human ResourcesUniversity of Hawaii at ManoaHonoluluHawaiiUSA
| | - Rui Guo
- School of Public HealthGuangxi Medical UniversityNanningChina
| | - Youping Deng
- Department of Quantitative Health SciencesJohn A. Burns School of Medicine, University of Hawaii at ManoaHonoluluHawaiiUSA
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Xu W, Che DD, Chen L, Lv SQ, Su J, Tan J, Liu Q, Pan YW. UBE2R2-AS1 Inhibits Xenograft Growth in Nude Mice and Correlates with a Positive Prognosis in Glioma. J Mol Neurosci 2021; 71:1605-1613. [PMID: 33528791 DOI: 10.1007/s12031-021-01793-y] [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: 09/24/2020] [Accepted: 01/04/2021] [Indexed: 10/22/2022]
Abstract
Our previous study showed that the lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis through the miR-877-3p/TLR4 pathway. In this study, it was further found that the expression of UBE2R2-AS1 in glioma tissues was decreased significantly, and gradually decreased with increasing clinical stage. Chi-square analysis showed that the expression of UBE2R2-AS1 was significantly correlated with the WHO stage of tumor and epilepsy. Using Kaplan-Meier univariate survival analysis, it was found that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma, while multiple Cox regression analysis showed that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma as a protective factor for glioma prognosis. The analysis of data from TCGA also showed that patients with high UBE2R2-AS1 levels or low miR-877-3p expression were more likely to have good survival outcomes. Further construction of a glioma xenograft model in nude mice showed that UBE2R2-AS1 overexpression inhibited the growth of tumors, and the inhibition of miR-877-3p expression had a similar effect. Simultaneous UBE2R2-AS1 overexpression and miR-877-3p inhibition further decreased the growth rate of tumors in nude mice. Taken together, the results of our study suggest that UBE2R2-AS1 is an important tumor suppressor gene in glioma, which may be a good marker and treatment target for the clinical detection of glioma.
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Affiliation(s)
- Wu Xu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.,Department of Neurosurgery, Affiliated Hospital of Jiujiang University, Jiujiang, 332000, Jiangxi, China
| | - Dan-Dan Che
- Department of Intensive Care Unit, Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518100, Guangdong, China
| | - Liang Chen
- Department of Neurosurgery, Affiliated Hospital of Jiujiang University, Jiujiang, 332000, Jiangxi, China
| | - Sheng-Qing Lv
- Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Jun Su
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jun Tan
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Qing Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Ya-Wen Pan
- Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China.
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Zhou X, Yuan Q, Zhang C, Dai Z, Du C, Wang H, Li X, Yang S, Zhao A. Inhibition of Japanese encephalitis virus proliferation by long non-coding RNA SUSAJ1 in PK-15 cells. Virol J 2021; 18:29. [PMID: 33509198 PMCID: PMC7841041 DOI: 10.1186/s12985-021-01492-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 01/07/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Japanese encephalitis virus is a mosquito-borne neurotropic flavivirus that causes acute viral encephalitis in humans. Pigs are crucial amplifier host of JEV. Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs) play important roles in virus infection. METHODS JEV proliferation was evaluated after overexpression or knockdown of lncRNA-SUSAJ1 using western blotting and reverse-transcription polymerase chain reaction (RT-PCR). C-C chemokine receptor type 1 (CCR1) was found to regulate the expression of lncRNA-SUSAJ1 by inhibitors screen. The expression of lncRNA-SUSAJ1 was detected using RT-PCR after overexpression or knockdown of transcription factor SP1. In addition, the enrichments of transcription factor SP1 on the promoter of lncRNA-SUSAJ1 were analyzed by chromatin immunoprecipitation. RESULTS In this study, we demonstrated that swine lncRNA-SUSAJ1 could suppress JEV proliferation in PK-15 cells. We also found that CCR1 inhibited the expression of lncRNA-SUSAJ1 via the transcription factor SP1. In addition, knockdown of CCR1 could upregulated the expression of SP1 and lncRNA-SUSAJ1, resulting in resistance to JEV proliferation. CONCLUSIONS These findings illustrate the importance of lncRNAs in virus proliferation, and reveal how this virus regulates lncRNAs in host cells to promote its proliferation.
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Affiliation(s)
- Xiaolong Zhou
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Qiongyu Yuan
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Chen Zhang
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Zhenglie Dai
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Chengtao Du
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Han Wang
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Xiangchen Li
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Songbai Yang
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China.
| | - Ayong Zhao
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China.
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Shi C, Zheng W, Wang J. lncRNA-CRNDE regulates BMSC chondrogenic differentiation and promotes cartilage repair in osteoarthritis through SIRT1/SOX9. Mol Cell Biochem 2021; 476:1881-1890. [PMID: 33479807 DOI: 10.1007/s11010-020-04047-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/26/2020] [Indexed: 12/19/2022]
Abstract
Osteoarthritis (OA) is the most common chronic and degenerative joint disease. Although traditional OA medications can partially relieve pain, these medications cannot completely cure OA. Therefore, it is particularly important to find an effective treatment for OA. This study explored the function of long non-coding RNA (lncRNA)-colorectal neoplasia differentially expressed gene (CRNDE) in the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the underlying molecular mechanism, aiming to develop a new treatment method for osteoarthritis. BMSCs were isolated from rat bone marrow using the gradient centrifugation method. And BMSC chondrogenic differentiation was induced with chondrogenic medium. The expression of lncRNA-CRNDE was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Silent information regulator factor 2-related enzyme 1 (SIRT1) and cartilage marker genes Aggrecan and collagen 2 (α1) protein expression were researched using western blot. Alcian blue staining was employed to examine the content of cartilage matrix proteoglycan glycosaminoglycan (GAG). The interaction between lncRNA-CRNDE and SIRT1 was detected by RNA pull-down and RNA immunoprecipitation (RIP) assay. Ubiquitination experiments were performed to measure the ubiquitination level of SIRT1. The combination between SMAD ubiquitination regulatory factor 2 (SMURF2) and SIRT1, as well as SRY-related high-mobility-group box 9 (SOX9) and collagen 2 (α1) promoter, was detected by Co-immunoprecipitation or ChIP. With the prolongation of induction time, the expression of lncRNA-CRNDE, SIRT1, cartilage marker genes Aggrecan and collagen 2 (α1) in BMSC osteogenic differentiation was gradually increased. Also, the content of cartilage matrix proteoglycan GAG was gradually elevated with the extension of the induction time. Further increase in the expression of SIRT1, cartilage marker genes Aggrecan and collagen 2 (α1) by overexpression of lncRNA-CRNDE also indicated elevated GAG content. RNA pull-down and RIP assay confirmed the binding between lncRNA-CRNDE and SIRT1. qRT-PCR and western blot showed that interference with lncRNA-CRNDE significantly inhibited the protein expression of SIRT1. BMSCs transfected with si-CRNDE increased ubiquitination levels of SIRT1 mediated by the E3 ligase SMURF2, leading to the reduced protein stability of SIRT1. However, overexpression of lncRNA-CRNDE increased the binding ability of SOX9 and collagen 2 (α1) promoter, which was reversed by the simultaneous transfection of CRNDE overexpression (pcDNA-CRNDE) and SIRT1 small interfering RNA (si-SIRT1). lncRNA-CRNDE regulates BMSC chondrogenic differentiation to promote cartilage repair in osteoarthritis through SIRT1/SOX9.
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Affiliation(s)
- Chengdi Shi
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. .,Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
| | - Wenhao Zheng
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.,Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
| | - Jinwu Wang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.,Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China
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Feng X, Huang E, Gao Y, Zhang Y, Zhou Y. The effects of NONRATT008453.2 on autophagy in genital tubercle fibroblasts of rats with hypospadias induced by dibutyl phthalate. Birth Defects Res 2021; 113:399-408. [PMID: 33452730 PMCID: PMC7986160 DOI: 10.1002/bdr2.1863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 11/26/2020] [Accepted: 12/20/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND Hypospadias is a common birth defect that might be caused by inadequate fusion of the urethral folds in the process of male external genital development. We intended to discover the crucial long noncoding RNAs (lncRNAs) regulating autophagy from the gene expression profile of the genital tubercle (GT) of dibutyl phthalate (DBP) induced hypospadiac rats. METHODS Whole transcriptome resequencing was used to determine the expression of the total RNA in GTs and cultured fibroblasts obtained from GTs of DBP-induced hypospadiac male rat fetuses. Autophagosomes and autolysosomes were examined under a transmission electron microscope after overexpression of lncRNA NONRATT008453.2 in the fibroblasts by adenovirus transfection. Finally, the protein expression levels of Atg5, Beclin-1, Atg7, and the LC3A/B-II:LC3A/B-I ratio were detected in the fibroblasts by western blotting. RESULTS NONRATT008453.2 suppressed autophagy by promoting the expression of Atg7, but inhibited the expressions of Atg5, Beclin-1, and the LC3A/B-II:LC3A/B-I ratio in the GT fibroblasts. CONCLUSIONS NONRATT008453.2 may have an influence on autophagy in the fibroblasts of the GT in DBP-induced hypospadiac rats.
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Affiliation(s)
- Xiao Feng
- Department of Clinical laboratory, Children's Hospital of Soochow University, Suzhou, P. R. China
| | - Enfu Huang
- Section of Pediatric Urology, Children's Hospital of Soochow University, Suzhou, P. R. China
| | - Yuanyuan Gao
- Department of Clinical laboratory, Children's Hospital of Soochow University, Suzhou, P. R. China
| | - Ya Zhang
- Central Laboratory of Pediatric Research Institute, Children's Hospital of Soochow University, Suzhou, P. R. China
| | - Yun Zhou
- Section of Pediatric Urology, Children's Hospital of Soochow University, Suzhou, P. R. China
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Qin J, Zhu T, Wu W, Chen H, He Y. Long Non-Coding RNA PCED1B-AS1 Promotes the Progression of Clear Cell Renal Cell Carcinoma Through miR-484/ZEB1 Axis. Onco Targets Ther 2021; 14:393-402. [PMID: 33469315 PMCID: PMC7813644 DOI: 10.2147/ott.s270149] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/21/2020] [Indexed: 12/14/2022] Open
Abstract
Background Long non-coding RNA (lncRNA) has been recognized as the new regulator and biomarker for cancers. However, in clear cell renal cell carcinoma (ccRCC), the functions of lncRNAs are not well characterized. This research aimed to probe the function of lncRNA PCED1B-AS1 in the progression of ccRCC. Materials and Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of PCED1B-AS1, microRNA-484 (miR-484), and zinc finger E-box binding homeobox 1 (ZEB1) in 40 pairs of human ccRCC tissues and corresponding adjacent kidney tissue samples. Chi-square test was employed to evaluate the association between PCED1B-AS1 expression level and clinicopathological characteristics. The effects of PCED1B-AS1, miR-484 and ZEB1 on the cell proliferation, migration and epithelial-mesenchymal transition (EMT) process of ccRCC cells were studied by CCK-8 assay, EdU cell proliferation assay, wound healing test and Western blotting. The regulatory relationships among PCED1B-AS1, miR-484, ZEB1 were examined by luciferase reporter gene assay and RNA immunoprecipitation assay. Results PCED1B-AS1 was remarkably up-regulated in ccRCC tissues and cell lines. High expression of PCED1B-AS1 was associated with poor prognosis of the patients. Loss-of-function experiments showed that PCED1B-AS1 could regulate the proliferation, migration and EMT of ccRCC cells. PCED1B-AS1 sponged miR-484 to suppress its expression, and miR-484 targeted the 3ʹ-UTR of ZEB1 to repress the expression of ZEB1. MiR-484 counteracted the functions of PCED1B-AS1 in promoting the proliferation, migration and EMT of ccRCC cells, and PCED1B-AS1 promotes the expression of ZEB1 via repressing miR-484. Conclusion PCED1B-AS1/miR-484/ZEB1 axis is involved in regulating the progression of ccRCC.
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Affiliation(s)
- Jianhua Qin
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Nephropathy, Luzhou 646000, Sichuan, People's Republic of China
| | - Tingting Zhu
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Nephropathy, Luzhou 646000, Sichuan, People's Republic of China
| | - Weihua Wu
- Department of Nephrology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Nephropathy, Luzhou 646000, Sichuan, People's Republic of China
| | - Huan Chen
- Department of Pathogen Biology, Basic Medical College, Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China
| | - Yi He
- Department of Urology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, People's Republic of China
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Zhu Z, Huang F, Xia W, Zeng H, Gao M, Li Y, Zeng F, He C, Chen J, Chen Z, Li Y, Cui Y, Chen H. Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA MALAT1 May Partially Contribute to Randall's Plaque Formation. Front Cell Dev Biol 2021; 8:596363. [PMID: 33505960 PMCID: PMC7829506 DOI: 10.3389/fcell.2020.596363] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/10/2020] [Indexed: 12/29/2022] Open
Abstract
Background The current belief is that Randall's plaques (RP) constitute a nidus for the formation of idiopathic calcium oxalate stones, but the upstream events in RP formation remain unclear. The present study aimed to investigate whether RP formation shares similarities with biomineralization and to illustrate the potential role played by the lncRNA MALAT1 in osteogenic differentiation of human renal interstitial fibroblasts (hRIFs). Materials and Methods Biomineralization and MALAT1 expression were assessed in RP, and hRIFs were isolated and induced under osteogenic conditions for further experiments. The transcription initiation and termination sites in MALAT1 were identified by 5' and 3' RACE. RNA immunoprecipitation assays and luciferase assays were used to validate the interactions among MALAT1, Runx2 and miRNAs. Results Upregulated expression of osteogenic markers and MALAT1 was observed in RP and hRIFs induced with osteogenic medium. Biomineralization in RP and calcium phosphate (CaP) deposits in induced hRIFs were further verified by electron microscopy. Furthermore, overexpression of MALAT1 promoted the osteogenic phenotype of hRIFs, while treatment with a miR-320a-5p mimic and knockdown of Runx2 significantly suppressed the osteogenic phenotype. Further analysis showed that MALAT1 functioned as a competing endogenous RNA to sponge miR-320a-5p, leading to upregulation of Runx2 and thus promoting osteogenic differentiation of hRIFs. Conclusion Ectopic calcification and MALAT1 partially contributed to the formation of RP, in which MALAT1 might promote Runx2 expression to regulate osteogenic differentiation of hRIFs by sponging miRNA-320a-5p. The current study sheds new light on the lncRNA-directed mechanism of RP formation via a process driven by osteogenic-like cells.
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Affiliation(s)
- Zewu Zhu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Fang Huang
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Weiping Xia
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Huimin Zeng
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Meng Gao
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Yongchao Li
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Feng Zeng
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Cheng He
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhiyong Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Yang Li
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Yu Cui
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Hequn Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
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Sharma K, Vignesh P, Srivastava P, Sharma J, Chaudhary H, Mondal S, Kaur A, Kaur H, Singh S. Epigenetics in Kawasaki Disease. Front Pediatr 2021; 9:673294. [PMID: 34249810 PMCID: PMC8266996 DOI: 10.3389/fped.2021.673294] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 06/01/2021] [Indexed: 12/17/2022] Open
Abstract
Kawasaki disease (KD) is a common febrile multisystemic inflammatory illness in children that preferentially affects coronary arteries. Children with KD who develop coronary artery aneurysms have a life-long risk of premature coronary artery disease. Hypothesis of inherent predisposition to KD is supported by epidemiological evidence that suggests increased risk of development of disease in certain ethnicities and in children with a previous history of KD in siblings or parents. However, occurrence of cases in clusters, seasonal variation, and very low risk of recurrence suggests an acquired trigger (such as infections) for the development of illness. Epigenetic mechanisms that modulate gene expression can plausibly explain the link between genetic and acquired predisposing factors in KD. Analysis of epigenetic factors can also be used to derive biomarkers for diagnosis and prognostication in KD. Moreover, epigenetic mechanisms can also help in pharmacogenomics with the development of targeted therapies. In this review, we analysed the available literature on epigenetic factors such as methylation, micro-RNAs, and long non-coding RNAs in KD and discuss how these mechanisms can help us better understand the disease pathogenesis and advance the development of new biomarkers in KD.
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Affiliation(s)
- Kaushal Sharma
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pandiarajan Vignesh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Priyanka Srivastava
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Jyoti Sharma
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Himanshi Chaudhary
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sanjib Mondal
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anupriya Kaur
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harvinder Kaur
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Surjit Singh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Feng J, Li J, Qie P, Li Z, Xu Y, Tian Z. Long non-coding RNA (lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating leucine zipper tumor suppressor (LZTS3) through sponging microRNA miR-1275. Bioengineered 2020; 12:196-207. [PMID: 33315502 PMCID: PMC8806334 DOI: 10.1080/21655979.2020.1860492] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
It is necessary to explore new molecules for the improvement of precise diagnosis and antitumor therapies in lung cancer. LncRNAs (long non-coding RNAs) play an important role in the regulation of cancer cell malignant behavior and tumor development. In this work, we found that a newly discovered lncRNA, lncRNA PGM5P4-AS1, was lower expressed in lung cancer tissues than adjacent tissues. Then, the lncRNA PGM5P4-AS1 was overexpressed or knocked-down in different lung cancer cells, and its effects on the malignant phenotypes were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, wound healing assay, and transwell assay. The results showed that the overexpression of PGM5P4-AS1 inhibited lung cancer cell proliferation, migration, and invasion activities, while these abilities were prominently promoted by the interference of PGM5P4-AS1. Further, the growth of lung cancer tumors in nude mice was also inhibited by PGM5P4-AS1 overexpression. In mechanism, PGM5P4-AS1 has the binding site of miR-1275 and could positively regulate the expression of LZTS3 via sponging miR-1275. In conclusion, PGM5P4-AS1 could be a potential precise diagnosis and therapeutic target biomarker of lung cancer.
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Affiliation(s)
- Junpeng Feng
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University , Shijiazhuang, P.R. China.,Department of Thoracic Surgery, Hebei Chest Hospital , Shijiazhuang, P.R. China
| | - Jianhang Li
- Department of Thoracic Surgery, Hebei Chest Hospital , Shijiazhuang, P.R. China
| | - Peng Qie
- Department of Thoracic Surgery, Hebei General Hospital , Shijiazhuang, P.R. China
| | - Zhenhua Li
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University , Shijiazhuang, P.R. China
| | - Yanzhao Xu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University , Shijiazhuang, P.R. China
| | - Ziqiang Tian
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University , Shijiazhuang, P.R. China
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Zhu L, He Y, Feng G, Yu Y, Wang R, Chen N, Yuan H. Genetic variants in long non-coding RNAs UCA1 and NEAT1 were associated with the prognosis of oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2020; 50:1131-1137. [PMID: 33384238 DOI: 10.1016/j.ijom.2020.11.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/18/2020] [Accepted: 11/12/2020] [Indexed: 12/24/2022]
Abstract
Oral squamous cell carcinoma (OSCC) is known for its high incidence, death rate, and relatively low 5-year survival. Long non-coding RNAs (lncRNAs) have been shown to play a significant role in cancerization and cancer progression. However, research on the association of polymorphisms in these lncRNAs with the prognosis of OSCC is lacking. Fifteen functional single-nucleotide polymorphisms (SNPs) in seven lncRNAs were selected to explore the relationship between these lncRNA SNPs and the prognosis among 209 OSCC patients. Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine the associations. Further functional exploration of significant SNPs was done by eQTL analysis. Using multivariate Cox hazards regression analysis, a predictive role of NEAT1 rs3741384 GG and UCA1 rs7255437 TC+TT in a worse prognosis of OSCC was identified. In addition, a marked increased risk of death was observed with an increasing number of unfavourable genotypes (NUG). The NUG was then incorporated with clinical variables in the receiver operating characteristic curve, and the results indicated a potential role of the NUG in predicting OSCC patient risk of death (area under the curve increase from 0.616 to 0.703). In conclusion, the study findings indicate that genetic variants rs3741384 in NEAT and rs7255437 in UCA1 may influence the survival of OSCC patients.
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Affiliation(s)
- L Zhu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China
| | - Y He
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, PR China
| | - G Feng
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China
| | - Y Yu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China
| | - R Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China
| | - N Chen
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China
| | - H Yuan
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Epidemiology and Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Centre, Nanjing Medical University, Nanjing, PR China.
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Chen H, Fan Y, Jing H, Tang S, Huang Z, Liao M, Lin S, Zhong J, Zhou J. LncRNA Gm12840 mediates WISP1 to regulate ischemia-reperfusion-induced renal fibrosis by sponging miR-677-5p. Epigenomics 2020; 12:2205-2218. [PMID: 33351669 DOI: 10.2217/epi-2020-0054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Aim: We aimed to identify that long noncoding RNAs (lncRNAs) are involved in ischemia-reperfusion (IR)-induced late fibrosis of kidney and may constitute novel therapeutic strategies for acute kidney injury-induced chronic kidney disease. Materials & methods: We performed the mouse model of IR later induced renal fibrosis and analyzed lncRNA profiles using second-generation sequencing during the pathogenesis. Results: The expression levels of 43 lncRNAs and 141 lncRNAs were respectively changed significantly 7 days and 2 weeks after IR treatment. Based on the correlation analysis of the differentially expressed genes, the interaction networks of lncRNAs, miRNAs and mRNA were structured. Conclusion: LncRNA (Gm12840) could act as a sponge for miR-677-5p to mediate fibroblast activation induced by TGF-β1 via the WISP1/PKB (Akt) signaling pathway.
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Affiliation(s)
- Hongtao Chen
- Department of Anesthesiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, 8 Huaying Road, Guangzhou, Guangdong 510060, PR China
| | - Youling Fan
- Department of Anesthesiology, Panyu Central Hospital, 8 Fuyu West Road, Guangzhou, Guangdong 511400, PR China
| | - Huan Jing
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Road, Guangzhou, Guangdong 510630, PR China
| | - Simin Tang
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Road, Guangzhou, Guangdong 510630, PR China
| | - Zhenxing Huang
- Department of Anesthesiology, The First People's Hospital of Foshan, 81 North Lingnan Avenue, Foshan, Guangdong 528000, PR China
| | - Meijuan Liao
- Department of Anesthesiology, The First People's Hospital of Foshan, 81 North Lingnan Avenue, Foshan, Guangdong 528000, PR China
| | - Sen Lin
- Department of Anesthesiology, The First People's Hospital of Foshan, 81 North Lingnan Avenue, Foshan, Guangdong 528000, PR China
| | - Jiying Zhong
- Department of Anesthesiology, The First People's Hospital of Foshan, 81 North Lingnan Avenue, Foshan, Guangdong 528000, PR China
| | - Jun Zhou
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Road, Guangzhou, Guangdong 510630, PR China
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Saba LM, Hoffman PL, Homanics GE, Mahaffey S, Daulatabad SV, Janga SC, Tabakoff B. A long non-coding RNA (Lrap) modulates brain gene expression and levels of alcohol consumption in rats. GENES BRAIN AND BEHAVIOR 2020; 20:e12698. [PMID: 32893479 PMCID: PMC7900948 DOI: 10.1111/gbb.12698] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/20/2020] [Accepted: 09/01/2020] [Indexed: 12/14/2022]
Abstract
LncRNAs are important regulators of quantitative and qualitative features of the transcriptome. We have used QTL and other statistical analyses to identify a gene coexpression module associated with alcohol consumption. The "hub gene" of this module, Lrap (Long non-coding RNA for alcohol preference), was an unannotated transcript resembling a lncRNA. We used partial correlation analyses to establish that Lrap is a major contributor to the integrity of the coexpression module. Using CRISPR/Cas9 technology, we disrupted an exon of Lrap in Wistar rats. Measures of alcohol consumption in wild type, heterozygous and knockout rats showed that disruption of Lrap produced increases in alcohol consumption/alcohol preference. The disruption of Lrap also produced changes in expression of over 700 other transcripts. Furthermore, it became apparent that Lrap may have a function in alternative splicing of the affected transcripts. The GO category of "Response to Ethanol" emerged as one of the top candidates in an enrichment analysis of the differentially expressed transcripts. We validate the role of Lrap as a mediator of alcohol consumption by rats, and also implicate Lrap as a modifier of the expression and splicing of a large number of brain transcripts. A defined subset of these transcripts significantly impacts alcohol consumption by rats (and possibly humans). Our work shows the pleiotropic nature of non-coding elements of the genome, the power of network analysis in identifying the critical elements influencing phenotypes, and the fact that not all changes produced by genetic editing are critical for the concomitant changes in phenotype.
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Affiliation(s)
- Laura M Saba
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Paula L Hoffman
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Gregg E Homanics
- Departments of Anesthesiology, Neurobiology and Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Spencer Mahaffey
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Swapna Vidhur Daulatabad
- Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA
| | - Sarath Chandra Janga
- Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA.,Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Boris Tabakoff
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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50
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Guan J, Liu P, Wang A, Wang B. Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia. Int J Mol Med 2020; 46:1490-1500. [PMID: 32700753 PMCID: PMC7447321 DOI: 10.3892/ijmm.2020.4683] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 05/26/2020] [Indexed: 12/13/2022] Open
Abstract
Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by the clonal accumulation of immature myeloid cells. Zinc finger E‑box binding homeobox 2 (ZEB2)‑antisense RNA 1 (AS1) has been verified to participate in the progression of several types of cancer, including AML. However, the potential mechanisms of ZEB2‑AS1 in AML have not yet been fully elucidated. The present study aimed to elucidate the role and regulatory mechanisms of ZEB2‑AS1 in AML. The expression of ZEB2‑AS1, microRNA‑122‑5p (miRNA/miR‑122‑5p) and polo‑like kinase 1 (PLK1) was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in AML tissues or cells. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) assay and apoptosis assay, respectively. The protein levels were examined by western blot analysis. The targeted sequence between miR‑122‑5p and ZEB2‑AS1 or PLK1 was predicted using an online database and verified by dual‑luciferase reporter assay. A mouse tumor xenograft model was established to confirm the effects of ZEB2‑AS1 on tumor growth in vivo. The results revealed that the expression levels of ZEB2‑AS1 and PLK1 were upregulated, while those of miR‑122‑5p were downregulated in AML tissues and cells. The knockdown of ZEB2‑AS1 inhibited proliferation and induced apoptosis in vitro, and inhibited tumor growth in vivo. By experimental verification, ZEB2‑AS1 was found to negatively regulate miR‑122‑5p expression and PLK1 was found to be a target gene of miR‑122‑5p. Furthermore, ZEB2‑AS1 was verified to regulate the expression of PLK1 by sponging miR‑122‑5p in AML cells. On the whole, the findings of the present study demonstrate that ZEB2‑AS1 promotes cell proliferation and inhibits apoptosis, at least partly by targeting PLK1 mediated by miR‑122‑5p in AML cells.
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MESH Headings
- Animals
- Apoptosis
- Cell Cycle Proteins/antagonists & inhibitors
- Cell Cycle Proteins/biosynthesis
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/physiology
- Cell Division
- Cell Line, Tumor
- Child
- Child, Preschool
- Female
- Gene Knockdown Techniques
- Genes, Reporter
- Heterografts
- Humans
- Leukemia, Myeloid, Acute/genetics
- Leukemia, Myeloid, Acute/pathology
- Male
- Mice
- Mice, Nude
- MicroRNAs/biosynthesis
- MicroRNAs/genetics
- MicroRNAs/physiology
- Neoplasm Proteins/antagonists & inhibitors
- Neoplasm Proteins/biosynthesis
- Neoplasm Proteins/genetics
- Neoplasm Proteins/physiology
- Protein Serine-Threonine Kinases/antagonists & inhibitors
- Protein Serine-Threonine Kinases/biosynthesis
- Protein Serine-Threonine Kinases/genetics
- Protein Serine-Threonine Kinases/physiology
- Proto-Oncogene Proteins/antagonists & inhibitors
- Proto-Oncogene Proteins/biosynthesis
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins/physiology
- RNA, Long Noncoding/biosynthesis
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/physiology
- RNA, Neoplasm/biosynthesis
- RNA, Neoplasm/genetics
- RNA, Neoplasm/physiology
- Signal Transduction/genetics
- Signal Transduction/physiology
- Polo-Like Kinase 1
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Affiliation(s)
- Jianmin Guan
- Department of Internal Medicine, Heze Medical College
| | - Ping Liu
- Department of Hematology, Heze Municipal Hospital
| | - Aixia Wang
- Department of Pharmacy, Chinese Medicine Hospital of Mudan District
| | - Bo Wang
- Department of Blood Transfusion, Heze Municipal Hospital, Heze, Shandong 274000, P.R. China
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