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Zhao L, Huang J, Fu X, Li Y, Wu S. IHNV induced miR-19-3p modulates immune response of rainbow trout (Oncorhynchus mykiss) by targeting DHX58-dependent RLR signaling pathway. FISH & SHELLFISH IMMUNOLOGY 2025; 160:110200. [PMID: 39954832 DOI: 10.1016/j.fsi.2025.110200] [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: 10/09/2024] [Revised: 01/16/2025] [Accepted: 02/12/2025] [Indexed: 02/17/2025]
Abstract
miR-19-3p has been implicated in various pathological and physiological processes, including immune response, inflammation, oncogenesis and cell damage. However, its function in rainbow trout (Oncorhynchus mykiss) has not been well elucidated. In this study, the expression patterns of miR-19-3p and target gene DExH-Box helicase 58 (DHX58) in rainbow trout infected with infectious hematopoietic necrosis virus (IHNV) were detected, and regulatory mechanism and function of miR-19-3p were investigated by overexpression and inhibition experiment in vitro and in vivo. Expression patterns showed that miR-19-3p and DHX58 displayed significant time-dependent changes in IHNV-infected rainbow trout intestines, skins, gills, and liver cells, and their expression were negatively correlated at multiple time points. In vitro, the targeting relationship between miR-19-3p and DHX58 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay, and overexpression of miR-19-3p significantly suppressed the expression of DHX58 and downstream genes interferon regulatory factor 3 (IRF3), interferon regulatory factor 7 (IRF7), interferon (IFN), myxovirus 1 (MX1), interferon-stimulated gene 15 (ISG15), nuclear factor kappa-B (NF-κB), and interleukin-1 beta (IL-1β), whereas the expression levels of DHX58 and downstream genes were significantly increased after transfecting miR-19-3p inhibitor. In vivo, agomiR-19-3p significantly inhibited the expression of DHX58, and then reduced the expression levels of IRF3, IRF7, IFN, MX1, NF-κB, IL-1β, tumor necrosis factor-α (TNFα), and ISG15. Additionally, overexpression of miR-19-3p significantly increased IHNV copies and cell proliferation number, and suppressed apoptosis, while the opposite results were obtained after miR-19-3p repressing. This study confirmed that miR-19-3p regulates rainbow trout antiviral immune by DHX58-mediated interferon pathway in vitro and in vivo, which provides potential for using miRNAs as anti-viral target drugs.
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Affiliation(s)
- Lu Zhao
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China
| | - Jinqiang Huang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China
| | - Xujuan Fu
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China
| | - Yongjuan Li
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China; College of Science, Gansu Agricultural University, Lanzhou, 730070, China.
| | - Shenji Wu
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China
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Rahman MS, Ghorai S, Panda K, Santiago MJ, Aggarwal S, Wang T, Rahman I, Chinnapaiyan S, Unwalla HJ. Dr. Jekyll or Mr. Hyde: The multifaceted roles of miR-145-5p in human health and disease. Noncoding RNA Res 2025; 11:22-37. [PMID: 39736851 PMCID: PMC11683234 DOI: 10.1016/j.ncrna.2024.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/14/2024] [Accepted: 11/09/2024] [Indexed: 01/01/2025] Open
Abstract
MicroRNAs (miRNAs) are classified as small, non-coding RNAs that play crucial roles in diverse biological processes, including cellular development, differentiation, growth, and metabolism. MiRNAs regulate gene expression by recognizing complementary sequences within messenger RNA (mRNA) molecules. Recent studies have revealed that miR-145-5p functions as a tumor suppressor in several cancers, including lung, liver, and breast cancers. Notably, miR-145-5p plays a vital role in the pathophysiology underlying HIV and chronic obstructive pulmonary diseases associated with cigarette smoke. This miRNA is abundant in biofluids and shows potential as a biomarker for the diagnosis and prognosis of several infectious diseases, such as hepatitis B, tuberculosis, and influenza. Additionally, numerous studies have indicated that other non-coding RNAs, including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate miR-145-5p. Given the significance of miR-145-5p, a comprehensive overview focusing on its roles in health and disease is essential. This review discusses the dual role of miR-145-5p as a protagonist and antagonist in important human diseases, with particular emphasis on disorders of the respiratory, digestive, nervous, reproductive, endocrine, and urinary systems.
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Affiliation(s)
- Md. Sohanur Rahman
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Suvankar Ghorai
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Kingshuk Panda
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Maria J. Santiago
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
- Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Saurabh Aggarwal
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Ting Wang
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
- Center for Translational Science, Florida International University, Port Saint Lucie, FL 34987, USA
| | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Srinivasan Chinnapaiyan
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Hoshang J. Unwalla
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
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Su F, Zhao W, Zhao F, Cao M, Zhu T, Lv W, Li B. Pyrococcus furiosus Argonaute-Based Fluorometric Biosensor for One-Tube Detection of Cancer-Associated Single Nucleotide Polymorphisms in MicroRNAs. Anal Chem 2025; 97:4678-4686. [PMID: 39982863 DOI: 10.1021/acs.analchem.4c07109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2025]
Abstract
MicroRNA-related single nucleotide polymorphisms (miR-SNPs) are promising biomarkers for cancer diagnostics, yet accurate detection methods remain limited. Here, we introduce a ligation-triggered Pyrococcus furiosus Argonaute (PfAgo) cleavage (LTAC) strategy for the sensitive detection of miR-SNPs, demonstrated using the rs11614913 SNP in miR-196a2, which is associated with nonsmall cell lung cancer (NSCLC). The mutant miR-196a2T serves as a scaffold for the formation of guide DNA (gDNA) catalyzed by the SplintR ligase, leading to PfAgo activation and enhanced fluorescence. In contrast, wild-type miR-196a2C cannot facilitate gDNA formation and thus fails to activate PfAgo. This method exhibits a linear relationship with the logarithm of the miR-196a2T concentration over a range of 0.2 pM to 100 nM, achieving a low detection limit of 0.15 pM. Analysis of NSCLC patient samples using LTAC reveals elevated levels of the rs11614913 SNP in miR-196a2 compared to healthy controls, underscoring the diagnostic potential of LTAC.
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Affiliation(s)
- Fengli Su
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 211166, China
| | - Wentao Zhao
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 211166, China
| | - Furong Zhao
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 211166, China
| | - Min Cao
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 211166, China
| | - Tianjiao Zhu
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 211166, China
| | - Wei Lv
- Department of Pharmacy, The Jiangyin Clinical College of Xuzhou Medical University, Jiangyin 214400, China
| | - Bingzhi Li
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 211166, China
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4
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Wu B, Zhang X, Zhao J, Zeng B, Cao Z. Identification and analysis of miRNA - mRNA regulatory modules associated with resistance to bacterial leaf streak in rice. BMC Genomics 2025; 26:207. [PMID: 40025448 PMCID: PMC11874638 DOI: 10.1186/s12864-025-11404-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 02/25/2025] [Indexed: 03/04/2025] Open
Abstract
BACKGROUND B: acterial leaf streak (BLS) is a bacterial disease that severely affects rice leaves, leading to significant yield reductions. microRNAs (miRNAs) are short non-coding RNAs extensively involved in the growth, development, and stress responses of plants and animals. However, miRNAs that regulate the response of rice to bacterial leaf streak are still relatively scarce. RESULTS: The indica rice variety Dular exhibits resistance to BLS, whereas the variety 9311 is highly susceptible to the disease. By conducting miRNA sequencing and transcriptome sequencing on both Dular and 9311 before and after BLS inoculation, we identified 19 miRNAs that were significantly downregulated at both 12 and 24 h post-inoculation in Dular, and 9 miRNAs that were significantly upregulated at the same time points in 9311. Additionally, through degradome sequencing, we identified 23 miRNA- mRNA regulatory modules that likely play crucial roles in rice resistance to BLS, and 4 miRNA- mRNA regulatory modules that may be important in rice susceptibility to the disease. DISCUSSION: Current studies on rice disease resistance miRNAs primarily focus on those involved in resistance to rice blast and bacterial blight, with the miRNA-target mRNA regulatory mechanisms for BLS remaining unclear. This study has identified miRNA-mRNA modules that may play significant roles in rice responses to BLS, contributing to the understanding of the miRNA regulatory network involved in rice defense against BLS infection.
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Affiliation(s)
- Baowei Wu
- Jiangxi Super-Rice Research and Development Center, Jiangxi Provincial Key Laboratory of Rice Germplasm Innovation and Breeding, Jiangxi Academy of Agricultural Sciences, National Engineering Research Center for Rice, Nanchang, 330200, China
| | - Xiaoyu Zhang
- National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research (Wuhan), Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China
| | - Jialiang Zhao
- Jiangxi Super-Rice Research and Development Center, Jiangxi Provincial Key Laboratory of Rice Germplasm Innovation and Breeding, Jiangxi Academy of Agricultural Sciences, National Engineering Research Center for Rice, Nanchang, 330200, China
| | - Bohong Zeng
- Jiangxi Super-Rice Research and Development Center, Jiangxi Provincial Key Laboratory of Rice Germplasm Innovation and Breeding, Jiangxi Academy of Agricultural Sciences, National Engineering Research Center for Rice, Nanchang, 330200, China
| | - Zhibin Cao
- Jiangxi Super-Rice Research and Development Center, Jiangxi Provincial Key Laboratory of Rice Germplasm Innovation and Breeding, Jiangxi Academy of Agricultural Sciences, National Engineering Research Center for Rice, Nanchang, 330200, China.
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Tesarova T, Fiala O, Hora M, Vaclavikova R. Non-coding transcriptome profiles in clear-cell renal cell carcinoma. Nat Rev Urol 2025; 22:151-174. [PMID: 39242964 DOI: 10.1038/s41585-024-00926-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/29/2024] [Indexed: 09/09/2024]
Abstract
Clear-cell renal cell carcinoma (ccRCC) is a common urological malignancy with an increasing incidence. The development of molecular biomarkers that can predict the response to treatment and guide personalized therapy selection would substantially improve patient outcomes. Dysregulation of non-coding RNA (ncRNA) has been shown to have a role in the pathogenesis of ccRCC. Thus, an increasing number of studies are being carried out with a focus on the identification of ncRNA biomarkers in ccRCC tissue samples and the connection of these markers with patients' prognosis, pathological stage and grade (including metastatic potential), and therapy outcome. RNA sequencing analysis led to the identification of several ncRNA biomarkers that are dysregulated in ccRCC and might have a role in ccRCC development. These ncRNAs have the potential to be prognostic and predictive biomarkers for ccRCC, with prospective applications in personalized treatment selection. Research on ncRNA biomarkers in ccRCC is advancing, but clinical implementation remains preliminary owing to challenges in validation, standardization and reproducibility. Comprehensive studies and integration of ncRNAs into clinical trials are essential to accelerate the clinical use of these biomarkers.
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Affiliation(s)
- Tereza Tesarova
- Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
- Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
| | - Ondrej Fiala
- Department of Oncology and Radiotherapeutics, Faculty of Medicine in Pilsen and University Hospital, Charles University, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Milan Hora
- Department of Urology, Faculty of Medicine in Pilsen and University Hospital, Charles University, Pilsen, Czech Republic
| | - Radka Vaclavikova
- Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic
- Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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Kawasumi R, Kawamura T, Yamashita K, Tominaga Y, Harada A, Ito E, Takeda M, Kita S, Shimomura I, Miyagawa S. Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells improves cardiac function through extracellular vesicle-mediated tissue repair in a rat model of ischemic cardiomyopathy. Regen Ther 2025; 28:253-261. [PMID: 39834593 PMCID: PMC11745812 DOI: 10.1016/j.reth.2024.12.008] [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: 10/27/2024] [Revised: 12/03/2024] [Accepted: 12/11/2024] [Indexed: 01/22/2025] Open
Abstract
Introduction Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) has a therapeutic effect on myocardial ischemia. However, the therapeutic mechanism underlying systemic iPS-MSC-based therapy for ischemic cardiomyopathy (ICM) remains unclear. We investigated the therapeutic effects of iPS-MSCs through extracellular vesicle (EV)-mediated tissue repair in a rat model of ICM. Methods A rat ICM model was created by left anterior descending coronary artery ligation. iPS-MSCs were administered intravenously every week for four weeks in the iPS-MSC group, whereas saline was administered to the control group. Alix, a protein involved in the biogenesis of EVs, was knocked down, and Alix-knockdown iPS-MSCs were administered to the siAlix group. We analyzed sequential cardiac function using echocardiography, histological analysis, cell tracking analysis with fluorescent dyes, and comprehensive RNA sequencing of the border zone of the myocardium after treatment. Results Left ventricular ejection fraction (LVEF) was significantly improved in the iPS-MSC group compared with that in the control group. In the siAlix group, LVEF was significantly lower than that in the iPS-MSC group. Histological analysis showed a significant decrease in fibrosis area and significant increase in microvascular density in the iPS-MSC group. A cell-tracking assay revealed iPS-MSC accumulation in the border zone of the myocardium during the acute phase. Comprehensive microRNA sequencing analysis revealed that EVs from iPS-MSCs contained miRNAs associated with anti-fibrosis and angiogenesis. Gene ontology analysis of differentially expressed genes in myocardial tissue also showed upregulation of pathways related to antifibrosis and neovascularization and downregulation of pathways linked to inflammation and T-cell differentiation. Conclusions Systemic administration of iPS-MSCs improved cardiac function through EV-mediated angiogenetic and antifibrotic effects in an ICM, suggesting the clinical possibility of treating chronic heart failure.
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Affiliation(s)
- Ryo Kawasumi
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takuji Kawamura
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kizuku Yamashita
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Yuji Tominaga
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Akima Harada
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Emiko Ito
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Maki Takeda
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Shunbun Kita
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
- Department of Adipose Management, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Iichiro Shimomura
- Department of Adipose Management, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shigeru Miyagawa
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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7
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Akbarzadeh A, Gerami MH, Farrokhi MR, Shapoori S, Jafarinia M. Therapeutic prospects of microRNAs derived from mesenchymal stem cell extracellular vesicles in rheumatoid arthritis: a comprehensive overview. Mol Cell Biochem 2025; 480:1275-1286. [PMID: 39105963 DOI: 10.1007/s11010-024-05082-1] [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: 04/17/2024] [Accepted: 07/29/2024] [Indexed: 08/07/2024]
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammatory joint damage. Recent studies have focused on the significance of microRNAs (miRNAs) in the pathogenesis of RA. Mesenchymal stem cells (MSCs) have emerged as a potential therapeutic option for RA based on their regenerative and immunomodulatory properties. MSCs release extracellular vesicles (EVs) containing miRNAs that can modulate immune and inflammatory responses. This article provides a comprehensive overview of the current evidence on the existence of various MSCs-derived miRNAs involved in the pathophysiology, characterization, and treatment of RA. An overview of the miRNA profiles in MSC-EVs is provided, along with an examination of their impact on various cell types implicated in RA pathogenesis, including synovial fibroblasts, macrophages, and T cells. Furthermore, the therapeutic capability of MSC-EVs for miRNA-based therapies in RA is discussed. In total, this review can present an extensive view of the complex interaction between EVs and MSC-derived miRNAs in RA and thus suggest valuable strategies for developing new therapeutic approaches to target this debilitating disease.
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Affiliation(s)
- Armin Akbarzadeh
- Department of Orthopedic Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Hadi Gerami
- Department of Orthopedic Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Majid Reza Farrokhi
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shima Shapoori
- Center for Research in Medical Devices (CÚRAM), University of Galway, Galway, Ireland
| | - Morteza Jafarinia
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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Qi Y, Yu J, Lou M, Yu Y, Li R, Zhang Z, Dai Y, Lao K, Cao M, Gou X. Lab on a single microbead: An enzyme-free strategy for the sensitive detection of microRNA via efficient localized catalytic hairpin assembly. Anal Chim Acta 2025; 1340:343659. [PMID: 39863312 DOI: 10.1016/j.aca.2025.343659] [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: 12/03/2024] [Accepted: 01/11/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Accurate quantification of microRNA (miRNA) is of great significance because it provides opportunities for the accurate early diagnosis of a series of human diseases including cancers. Currently, complicated nucleic acid amplification technologies are always required for the highly sensitive miRNA detection. The introduction of nucleic acid signal amplification coupled with various enzymes will inevitably lead to tedious work and increase the complexity of the analysis process. It is still urgently desired to develop enzyme-free yet sensitive assays that enable the sensitive analysis of miRNA in complicated biological samples. RESULTS A single microbead (MB)-based localized catalytic hairpin assembly (CHA) strategy is proposed for the sensitive analysis of microRNA (miRNA). This rationally designed CHA strategy allows target miRNA to walk only on a single MB which can create a micro-amplification zone, initiating a highly efficient localized CHA reaction, generating a large number of fluorescent DNA duplexes on the surface of single MB. The efficient localized CHA on single MB can not only greatly suppress the nonspecific reaction between two hairpin probes, thus decreasing the background signal, but also greatly enhance the brightness of MB owing to the highly-concentrated fluorescence enrichment on only one MB. Therefore, highly sensitive quantification of miRNA has been achieved by measuring the fluorescence signal on MB using a confocal fluorescence microscope. This new strategy exhibits a detection limit of 1.09 pM for let-7a detection, and enables high specificity of distinguishing homologous miRNA family members. SIGNIFICANCE This is the first report by only using one single MB as a carrier to conduct localized CHA, rendering highly-concentrated fluorescence enrichment on only one MB and a dramatic increase in sensitivity. This single MB-based localized CHA strategy has been successfully applied to the accurate analysis of miRNA target in complex biological sample.
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Affiliation(s)
- Yan Qi
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Jiangtao Yu
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Ming Lou
- Stomatology College of Xi'an Medical University, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Yameng Yu
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Ruohan Li
- Yantai Yongqi Technical Consulting Service Co., Ltd., Yantai, 264003, Shandong Province, PR China
| | - Zhenhao Zhang
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Yuxuan Dai
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Kejing Lao
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Meng Cao
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China
| | - Xingchun Gou
- Institute of Basic and Translational Medicine & Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China; Engineering Research Center of Brain Diseases Drug Development, Universities of Shaanxi Province, Xi'an Medical University, Xi'an, 710021, Shaanxi Province, PR China.
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Yin C, Liufu C, Ye S, Zhu T, Jiang J, Wang M, Zhou L, Yao L, Wang Y, Shi B. Tumor-derived exosomal KPNA2 activates fibroblasts and interacts with KIFC1 to promote bladder cancer progression, a process inhibited by miR-26b-5p. Cell Mol Biol Lett 2025; 30:20. [PMID: 39956902 PMCID: PMC11830183 DOI: 10.1186/s11658-025-00687-w] [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: 07/09/2024] [Accepted: 01/07/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Recent studies have illuminated the complexities of treating advanced bladder cancer (BCa), underscoring the importance of comprehending its molecular mechanisms for creating novel therapies. While the role of Karyopherin a2 (KPNA2) in promoting BCa growth is established, the precise mechanism remains elusive. METHODS To investigate the regulatory role of KPNA2 in BCa, we employed a comprehensive approach integrating clinical case data and bioinformatics analysis to evaluate the expression of KPNA2 in BCa tissues. Mechanisms promoting cancer by KPNA2 were examined using both in vivo and in vitro models. RESULTS Our research reveals that miR-26b-5p acts as an anticancer factor by targeting and inhibiting KPNA2 expression. Furthermore, we have observed that the interaction between KPNA2 and Kinesin Family Member C1 (KIFC1) facilitates the transition of BCa cells into the G2/M phase, thereby promoting tumor advancement via activation of the Phosphoinositide 3-kinase (PI3K)- Protein Kinase B (AKT) pathway. Importantly, this investigation is the first to identify KPNA2 expression in exosomes originating from BCa tissues. Plasma exosomes from patients with BCa exhibited notably increased levels of KPNA2 compared with healthy controls, suggesting KPNA2 as a potential new tumor indicator. Additionally, KPNA2 from BCa cells triggered the conversion of fibroblasts into cancer-associated fibroblasts (CAFs), which secreted elevated levels of interleukin-6 (IL-6), contributing to a tumor-supporting environment. CONCLUSIONS These findings suggest that KPNA2 is a key gene that promotes BCa progression, can potentially be a novel tumor marker, and may serve as a new therapeutic target for BCa.
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Affiliation(s)
- Cong Yin
- Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, No. 3002, Sungangxi Road, Shenzhen, 518035, People's Republic of China
- Shenzhen University Health Science Center, Shenzhen, 518055, China
| | - Cen Liufu
- Shantou University Medical College, Shantou, 515041, China
- Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China
| | - Shuai Ye
- Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, No. 3002, Sungangxi Road, Shenzhen, 518035, People's Republic of China
- Shenzhen University Health Science Center, Shenzhen, 518055, China
| | - Tao Zhu
- Shantou University Medical College, Shantou, 515041, China
- Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China
| | - Jiahao Jiang
- Department of Urology, Shenzhen Second People's Hospital, Clinical College of Anhui Medical University, Shenzhen, 518035, China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, 230032, Anhui, China
| | - Mingxia Wang
- Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China
| | - Liqun Zhou
- Department of Urology, Peking University First Hospital, No. 8 Xishiku St., Xicheng District, Beijing, 100034, People's Republic of China
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, No. 8 Xishiku St., Xicheng District, Beijing, 100034, China
| | - Lin Yao
- Department of Urology, Peking University First Hospital, No. 8 Xishiku St., Xicheng District, Beijing, 100034, People's Republic of China.
- Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, No. 8 Xishiku St., Xicheng District, Beijing, 100034, China.
| | - Yan Wang
- Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China.
| | - Bentao Shi
- Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, No. 3002, Sungangxi Road, Shenzhen, 518035, People's Republic of China.
- Shenzhen University Health Science Center, Shenzhen, 518055, China.
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10
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Huang L, Liao C, Xiong Z, Chen Z, Zhang S. Hsa-miR-526b-5p Regulates the Sensitivity of Colorectal Cancer to 5-Fluorouracil by Targeting TP53 in Organoid Models. Biochem Genet 2025:10.1007/s10528-025-11045-y. [PMID: 39953363 DOI: 10.1007/s10528-025-11045-y] [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: 06/06/2024] [Accepted: 01/27/2025] [Indexed: 02/17/2025]
Abstract
This study aimed to explore the mechanisms through which microRNAs (miRNAs) regulate 5-fluorouracil (5-FU) sensitivity in colorectal cancer (CRC) using organoid models. Fresh tissue samples from CRC tumors were collected, and CRC organoids were isolated and cultured. The consistency between CRC organoids and their derived tissues was validated. CRC organoids were treated with 5-FU, and ATP activity was measured. High-throughput sequencing of CRC organoids, combined with Gene Expression Omnibus (GEO) data analysis, was performed to examine miRNA expression following 5-FU treatment. Next, we investigated the cellular function of miR-526b-5p in CRC organoids and cells. Dual-luciferase reporter assays validated the binding of miR-526b-5p to the 3' UTR of TP53 mRNA. We successfully established CRC organoids that exhibited characteristics consistent with their source tissues. 5-FU treatment suppressed the proliferation and ATP activity of CRC organoids. High-throughput sequencing of CRC organoids, combined with GEO data analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation, revealed that hsa-miR-526b-5p levels were elevated following 5-FU treatment in CRC organoids and cells. Furthermore, hsa-miR-526b-5p was upregulated in CRC tissues compared to adjacent normal tissues, correlating with poor survival in CRC patients. Overexpression of hsa-miR-526b-5p mitigated the inhibitory effects of 5-FU on CRC organoid proliferation, migration, invasion, and ferroptosis. In contrast, silencing of hsa-miR-526b-5p impaired cell function and ferroptosis. Additionally, overexpression of hsa-miR-526b-5p decreased TP53 mRNA and protein levels while increasing the expression of SLC7A11 mRNA and protein. Silencing of hsa-miR-526b-5p resulted in the opposite effect. hsa-miR-526b-5p directly targeted and inhibited TP53 expression. Overexpression of TP53 diminished the promotive effect of hsa-miR-526b-5p on ferroptosis-related proteins GPX4 and SLC7A11, whereas inhibition of TP53 reversed the impact of hsa-miR-526b-5p silencing. Our study demonstrates that hsa-miR-526b-5p targets TP53 to regulate 5-FU sensitivity in CRC through the ferroptosis pathway based on CRC organoid models.
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Affiliation(s)
- Lizhe Huang
- Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, China
| | - Cun Liao
- Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, China
| | - Zuming Xiong
- Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, China
| | - Zhongyang Chen
- Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, China
| | - Sen Zhang
- Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, China.
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11
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Balali MR, Taghizadeh M, Alizadeh M, Karami Y, Karimi F, Khatami SH, Taheri-Anganeh M, Ehtiati S, Movahedpour A, Mahmoudi R, Ghasemi H. MicroRNA biosensors for detection of chronic kidney disease. Clin Chim Acta 2025; 567:120081. [PMID: 39653321 DOI: 10.1016/j.cca.2024.120081] [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: 10/06/2024] [Revised: 12/04/2024] [Accepted: 12/04/2024] [Indexed: 12/13/2024]
Abstract
Chronic kidney disease (CKD) is a prevalent health condition characterized by gradual kidney function loss. Early detection is crucial for the effective management and treatment of CKD. A promising biomarker for various diseases, including chronic kidney disease, is microRNAs (miRNAs), which are becoming increasingly important due to their stability and differential expression in various disease-related states, including CKD. Recent developments in microRNA biosensors have made it possible to detect miRNAs associated with CKD in a sensitive and specific manner. This review article discusses the current state of microRNA biosensors for detecting CKD and highlights their potential applications in clinical settings. Various microRNA biosensors, including electrochemical, optical, and nanomaterial-based sensors, are explored for their ability to detect specific miRNAs linked to CKD progression. The advantages and limitations of these biosensors are evaluated, focusing on factors such as sensitivity, specificity, and ease of use. Overall, microRNA biosensors are promising diagnostic tools for early detection of CKD. However, challenges such as standardizing protocols, validating in large cohorts, and translating to clinical practice remain to be addressed. Future research efforts should aim to overcome these limitations to fully realize the potential of microRNA biosensors in improving the diagnosis and management of CKD.
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Affiliation(s)
| | - Mohammad Taghizadeh
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Alizadeh
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yousof Karami
- Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | | | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Sajad Ehtiati
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Movahedpour
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Reza Mahmoudi
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran.
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12
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Li Y, Chen S, Rao H, Cui S, Chen G. MicroRNA Gets a Mighty Award. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2414625. [PMID: 39836690 PMCID: PMC11831481 DOI: 10.1002/advs.202414625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/29/2024] [Indexed: 01/23/2025]
Abstract
Recent advancements in microRNAs (miRNAs) research have revealed their key roles in both normal physiological processes and pathological conditions, leading to potential applications in diagnostics and therapeutics. However, the path forward is fraught with several scientific and technical challenges. This review article briefly explores the milestones of the discovery, biogenesis, functions, and application for clinical diagnostic and therapeutic strategies of miRNAs. The potential challenges and future directions are also discussed to fully harness their capabilities.
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Affiliation(s)
- Yu Li
- Department of Human Cell Biology and GeneticsJoint Laboratory of Guangdong‐Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong518055China
| | - Sijie Chen
- Department of Human Cell Biology and GeneticsJoint Laboratory of Guangdong‐Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong518055China
| | - Hai Rao
- Department of BiochemistryKey University Laboratory of Metabolism and Health of GuangdongSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong518055China
| | - Shengjin Cui
- Clinical LaboratoryThe University of Hong Kong‐Shenzhen HospitalShenzhenGuangdong518053China
| | - Guoan Chen
- Department of Human Cell Biology and GeneticsJoint Laboratory of Guangdong‐Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong518055China
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13
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De Sousa P, Seitz H. [Nobel Prize in physiology or medicine 2024: Victor Ambros and Gary Ruvkun - The discovery of microRNAs, revealing a New World in genetics]. Med Sci (Paris) 2025; 41:180-185. [PMID: 40028957 DOI: 10.1051/medsci/2025012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2025] Open
Abstract
Le prix Nobel 2024 de physiologie ou médecine a récompensé Victor Ambros et Gary Ruvkun pour leur découverte du premier microARN en 1993. Attirés par le phénotype intriguant d’un mutant du ver nématode Cænorhabditis elegans, dont le gène muté semblait échapper aux méthodes habituelles d’identification, les deux chercheurs et leurs équipes ont mis au jour une nouvelle classe de régulateurs de l’expression des gènes. Leurs découvertes, admirables de rigueur et de clairvoyance (leurs articles de 1993 révélaient déjà plusieurs des propriétés essentielles des microARN), sont trop longtemps restées négligées par la communauté scientifique, avant de susciter un véritable engouement quelques années plus tard.
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Affiliation(s)
- Pauline De Sousa
- Institut de génétique humaine, UMR 9002 CNRS et Université de Montpellier, Montpellier, France
| | - Hervé Seitz
- Institut de génétique humaine, UMR 9002 CNRS et Université de Montpellier, Montpellier, France
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14
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Yamamoto K, Chiba M. MicroRNA‑21‑5p expression in extracellular vesicles is increased in the blood of aging mice and in vascular endothelial cells induced by ionizing radiation. Exp Ther Med 2025; 29:22. [PMID: 39650777 PMCID: PMC11621913 DOI: 10.3892/etm.2024.12772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 10/25/2024] [Indexed: 12/11/2024] Open
Abstract
In recent years, the Japanese population has been aging and the risk of contracting various age-related diseases has increased. Thus, there is a need to analyze components that are characteristic of aging and examine their association with diseases to detect age-related diseases at an early stage. In the present study, microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) of 82-102-week-old mice were analyzed to identify miRNAs characteristic of aging. Increased expression of mmu-miR-21a-5p was observed. These miRNAs may be derived from senescent vascular endothelial cells, and RNA-sequencing data (GSE130727) of HUVECs induced to senesce by 4 Gy of radiation revealed that the miRNAs were involved in the cell cycle and DNA repair. Annotations to senescence-related pathways were also identified. Reduced expression of the miR-21-5p target gene, which has an identical sequence in humans and mice, was confirmed. In HUVECs induced to age under similar conditions, increased senescence-associated β-galactosidase activity and increased intracellular miR-21-5p expression were observed. A portion of the miR-21-5p was secreted extracellularly by internalizing tetraspanin-positive EVs, and miR-21-5p was secreted into the extracellular space. The present study also demonstrated that miR-21-5p expression was upregulated and extracellular secretion of miR-21-5p was enhanced during vascular endothelial cell senescence. These findings suggested that increased serum miR-21-5p represents a biomarker for vascular endothelial cell senescence.
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Affiliation(s)
- Keisuke Yamamoto
- Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Mitsuru Chiba
- Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
- Research Center for Biomedical Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
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15
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Su J, Liu T, Wang M, Xu W, Liu J, Lan J, Chen Y, Xu H, Guo D, Lai Z. Enhanced stability of hairpin-functionalized DNA tetrahedral nanostructures for miRNA detection in plasma from ischemic stroke patients. Anal Chim Acta 2025; 1334:343419. [PMID: 39638466 DOI: 10.1016/j.aca.2024.343419] [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: 10/17/2024] [Revised: 11/06/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024]
Abstract
The enzyme-free amplification technique using the Hybridization Chain Reaction (HCR) is gaining traction for its efficiency in miRNA analysis. Conventional HCR (C-HCR) with hairpin probes faces challenges due to enzymatic degradation in body fluids, leading to potential false-positive results. This study addresses the critical need for a more reliable method that resists enzymatic breakdown and improves diagnostic accuracy for detecting miRNA related to ischemic stroke. We have developed a novel DNA tetrahedral nanostructures-mediated HCR (DTN-HCR) platform for the precise detection of microRNA-25 (miR-25), a biomarker for ischemic stroke. Incorporating two unique DNA tetrahedral nanostructures with embedded hairpin structures (DTN-HP1 and DTN-HP2), this platform activates upon miR-25 binding, initiating a robust DTN-HCR reaction. This reaction forms extensive DNA tetrahedron clusters that significantly boost the fluorescence signal, enabling detection thresholds as low as 5.4 pM. The method showcases exceptional specificity by distinguishing target miRNA from close analogues and maintains structural integrity against DNase I and fetal bovine serum (FBS), verified through polyacrylamide gel electrophoresis (PAGE). It successfully differentiates ischemic stroke patients from healthy controls by analyzing peripheral blood-derived miRNAs. This study concludes that the DTN-HCR platform substantially enhances the specificity and stability of miRNA detection, marking a significant advancement in non-enzymatic miRNA analysis techniques. With its capability to accurately identify ischemic stroke biomarkers at very low concentrations and its resistance to enzymatic degradation, the DTN-HCR method presents a valuable diagnostic tool for ischemic stroke, potentially improving early detection and monitoring in a clinical environment.
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Affiliation(s)
- Jiansheng Su
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China
| | - Tingshan Liu
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China
| | - Min Wang
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China
| | - Wansong Xu
- College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China
| | - Junle Liu
- Department of Anesthesiology, Xiamen Third Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Xiamen, Fujian, 361199, China
| | - Jianning Lan
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China
| | - Yujuan Chen
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China
| | - Huo Xu
- College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China.
| | - Danhua Guo
- Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou, Fujian, 350001, China.
| | - Zhongmeng Lai
- Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
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16
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Chen Z, Chen W, Xu C, Song H, Ji X, Jiang H, Duan H, Li Z, Gao W, Yao T, Zhang Z, He L, Yin Y, Yang N, Tian W, Wu J, Li X. Near-infrared fluorogenic RNA for in vivo imaging and sensing. Nat Commun 2025; 16:518. [PMID: 39788937 PMCID: PMC11718054 DOI: 10.1038/s41467-024-55093-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 11/29/2024] [Indexed: 01/12/2025] Open
Abstract
Fluorogenic RNA aptamers have various applications, including use as fluorescent tags for imaging RNA trafficking and as indicators of RNA-based sensors that exhibit fluorescence upon binding small-molecule fluorophores in living cells. Current fluorogenic RNA:fluorophore complexes typically emit visible fluorescence. However, it is challenging to develop fluorogenic RNA with near-infrared (NIR) fluorescence for in vivo imaging and sensing studies. To address this issue, we identify and modulate red fluorescent protein-like fluorophores to bind Squash, a highly folded fluorogenic RNA. One of these fluorophores, DFQL-1T, exhibits photostable NIR fluorescence when bound to Squash, enabling RNA visualization in living mammalian cells and mice. With Squash:DFQL-1T complexes, we generate RNA-based sensors for detecting non-coding RNAs and small molecule targets in living mammalian cells and in mice. These studies reveal a fluorogenic RNA:fluorophore complex that can be readily developed into NIR fluorescent RNA tags for in vivo imaging and sensing.
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Affiliation(s)
- Zhenyin Chen
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- Department of Pulmonary and Critical Care Medicine, the Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China
- University of Chinese Academy of Sciences, 100049, Beijing, China
| | - Wei Chen
- Centre for Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, China
- Hengyang Key Laboratory of Cellular Stress Biology, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China
| | - Cun Xu
- Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 130012, Changchun, China
| | - Haozhi Song
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
| | - Xin Ji
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
| | - Haodong Jiang
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- University of Chinese Academy of Sciences, 100049, Beijing, China
| | - Hongtao Duan
- College of Life Sciences, Hebei University, 071002, Baoding, Hebei, China
| | - Zehao Li
- College of Life Sciences, Hebei University, 071002, Baoding, Hebei, China
| | - Wankai Gao
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
| | - Tuoxin Yao
- College of Life Sciences, Hunan Normal University, 410081, Changsha, China
| | - Zhongxuan Zhang
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- University of Chinese Academy of Sciences, 100049, Beijing, China
| | - Liuqin He
- College of Life Sciences, Hunan Normal University, 410081, Changsha, China
| | - Yulong Yin
- Yuelushan Laboratory, 410128, Changsha, China
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Nanyang Yang
- Centre for Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, China
| | - Wenjing Tian
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 130012, Changchun, China
| | - Jiahui Wu
- Department of Chemistry, University of Massachusetts, 01003, Amherst, MA, USA
| | - Xing Li
- Interdisciplinary Science Center, State Key Laboratory of Integrated Management of Pest Insects and Rodents,Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
- Department of Pulmonary and Critical Care Medicine, the Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China.
- College of Life Sciences, Hebei University, 071002, Baoding, Hebei, China.
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17
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Wu H, Lyu X, Xu M, Chen Y, Liao S, Zhang G, Lin Y, Cai X. A Multifunctional miRNA Delivery System Based on Tetrahedral Framework Nucleic Acids for Regulating Inflammatory Periodontal Ligament Stem Cells and Attenuating Periodontitis Bone Loss. ACS APPLIED MATERIALS & INTERFACES 2025; 17:560-571. [PMID: 39679863 DOI: 10.1021/acsami.4c17195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
Periodontitis is a chronic inflammatory disease that leads to periodontal tissue damage and tooth loss. Therefore, controlling inflammatory bone loss and promoting osteogenesis is a crucial challenge clinically. MicroRNA (miRNA) based gene therapy has shown substantial prospects in recent years, but its application has been limited due to structural instability and easy degradation by enzymes. Research has shown that miRNA-200c is regarded as a key miRNA by regulating multiple signaling pathways during the process of bone resorption. Tetrahedral framework nucleic acid (tFNA) can be considered an ideal carrier of miRNA due to its good tissue permeability, cell uptake efficiency, and biocompatibility. This study developed a tFNA system carrying miR-200c, named T-200c, to exert various biological effects in human periodontal ligament stem cells (PDLSCs). The activation of the NF-κB pathway is diminished, whereas the Akt/β-catenin pathway is enhanced, resulting in a notable decrease in the release of diverse inflammatory mediators and cellular reactive oxygen species. This modulation fosters cell proliferation and osteogenic differentiation, thereby rejuvenating the functionality of PDLSCs. These changes offer a viable alternative for the treatment of periodontitis and the regeneration of periodontal tissues.
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Affiliation(s)
- Haoyan Wu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xiaoying Lyu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Mengzhuo Xu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Ye Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Shengnan Liao
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Geru Zhang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yunfeng Lin
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
- Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan 610041, China
- National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xiaoxiao Cai
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
- Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan 610041, China
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18
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Marceca GP, Romano G, Acunzo M, Nigita G. ncRNA Editing: Functional Characterization and Computational Resources. Methods Mol Biol 2025; 2883:455-495. [PMID: 39702721 DOI: 10.1007/978-1-0716-4290-0_20] [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] [Indexed: 12/21/2024]
Abstract
Non-coding RNAs (ncRNAs) play crucial roles in gene expression regulation, translation, and disease development, including cancer. They are classified by size in short and long non-coding RNAs. This chapter focuses on the functional implications of adenosine-to-inosine (A-to-I) RNA editing in both short (e.g., miRNAs) and long ncRNAs. RNA editing dynamically alters the sequence and structure of primary transcripts, impacting ncRNA biogenesis and function. Notable findings include the role of miRNA editing in promoting glioblastoma invasiveness, characterizing RNA editing hotspots across cancers, and its implications in thyroid cancer and ischemia. This chapter also highlights bioinformatics resources and next-generation sequencing (NGS) technologies that enable comprehensive ncRNAome studies and genome-wide RNA editing detection. Dysregulation of RNA editing machinery has been linked to various human diseases, emphasizing the potential of RNA editing as a biomarker and therapeutic target. This overview integrates current knowledge and computational tools for studying ncRNA editing, providing insights into its biological significance and clinical applications.
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Affiliation(s)
| | - Giulia Romano
- Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mario Acunzo
- Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Giovanni Nigita
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
- Center for RNA Biology, The Ohio State University, Columbus, OH, USA.
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19
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Uno H, Takeuchi H, Abe I, Yoshino T, Taguchi T, Hirakawa Y, Matsunaga T, Tanaka T. PCR- and wash-free detection of serum miRNA via signaling probe hybridization. Biotechnol Bioeng 2025; 122:159-166. [PMID: 39397338 DOI: 10.1002/bit.28859] [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: 07/23/2024] [Revised: 09/26/2024] [Accepted: 09/30/2024] [Indexed: 10/15/2024]
Abstract
Detection of microRNAs (miRNAs) in the serum is an effective liquid biopsy technique for cancer diagnosis. However, conventional diagnostic methods are time-consuming and complex. Therefore, in this study, we established a signaling probe-based DNA microarray system for miRNA detection. PCR, fluorescence labeling, and washing are not necessary for signaling probes. Four probes were designed using different miRNAs as diagnostic cancer markers. The developed system is useful for various miRNAs, regardless of their target lengths (18-26-mer) and GC content (36%-89%). Here, all the assays were performed within 40 min. Overall, our signaling probe-based DNA hybridization system facilitates the simple and rapid detection of serum miRNAs without the need for gene amplification, fluorescence labeling and washing.
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Affiliation(s)
- Haruka Uno
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Hiyori Takeuchi
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Ishin Abe
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Tomoko Yoshino
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | | | - Yuko Hirakawa
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
- Yokogawa Electric Corporation, Tokyo, Japan
| | - Tadashi Matsunaga
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Tsuyoshi Tanaka
- Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan
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20
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Tian J, He Y, Zhang Z, Zhu Y, Ren H, Zhang L, Li L, Li W, Zhang W, Xiao T, Zhou H, Li X. miR-224-5p Suppresses Non-Small Cell Lung Cancer via IL6ST-Mediated Regulation of the JAK2/STAT3 Pathway. Thorac Cancer 2025; 16:e15516. [PMID: 39840666 PMCID: PMC11751714 DOI: 10.1111/1759-7714.15516] [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: 08/25/2024] [Revised: 11/14/2024] [Accepted: 12/04/2024] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Our study aimed to explore the specific functions and potential mechanisms of miR-224-5p in non-small cell lung cancer (NSCLC). METHODS We first analyzed the expression of miR-224-5p in NSCLC patients and cell lines through the GEO database and qRT-PCR analysis. Then, we used MTT assays, wound healing assays, Transwell assays, and western blotting to evaluate the effects of miR-224-5p on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we used a xenograft tumor model to evaluate the effect of miR-224-5p on NSCLC tumor growth. Potential binding targets of miR-224-5p were further identified through the target prediction databases, and the relationships between miR-224-5p, its targets, and downstream signaling pathways were further verified using luciferase reporter gene assays and western blotting. RESULTS The GEO database and qRT-PCR analysis indicated that miR-224-5p was significantly downregulated in NSCLC patients and cell lines. Functional assays indicated that inhibiting miR-224-5p could enhance the proliferation, migration, invasion, and EMT of NSCLC cells, as well as accelerate tumor growth. In contrast, overexpression of miR-224-5p inhibited these processes. We identified IL6ST (interleukin 6 signal transducer) as a binding target of miR-224-5p. We observed that miR-224-5p could bind to and inhibit IL6ST expression and JAK2/STAT3 signaling pathway, and the inhibition of NSCLC tumor growth and JAK2/STAT3 pathway by miR-224-5p could be reversed by IL6ST overexpression. CONCLUSION Our study demonstrated that miR-224-5p inhibited NSCLC by targeting IL6ST, thereby downregulating the JAK2/STAT3 signaling pathway.
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Affiliation(s)
- Jiao Tian
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Yiming He
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Zihui Zhang
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Yuxin Zhu
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Haixia Ren
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Liang Zhang
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Lei Li
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Wei Li
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Weidong Zhang
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Ting Xiao
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
- State Key Laboratory of Separation Membranes and Membrane Processes, Tianjin Key Laboratory of Green Chemical Technology and Process Engineering, School of Pharmaceutical SciencesTiangong UniversityTianjinChina
| | - Honggang Zhou
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
| | - Xiaoping Li
- Department of Thoracic Surgery, Tianjin First Central Hospital, School of MedicineNankai UniversityTianjinChina
- State Key Laboratory of Medicinal Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjinChina
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Quah S, Subramanian G, Tan JSL, Utami KH, Sampath P. MicroRNAs: a symphony orchestrating evolution and disease dynamics. Trends Mol Med 2025; 31:21-35. [PMID: 39112313 DOI: 10.1016/j.molmed.2024.07.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 06/13/2024] [Accepted: 07/08/2024] [Indexed: 01/11/2025]
Abstract
The genesis of human disease lies in our evolutionary past. Evolution has featured a general trend towards increased morphological complexity, partly conferred by expansion in gene regulatory capacity via microRNA (miRNA) innovation. Many human diseases are directly related to the evolved roles of these miRNAs, and miRNA-based therapies are emerging as an appealing strategy for precision medicine. We focus on three categories of human disease - cancer, inflammation-linked pathologies, and neurological disorders - which are highly prevalent and are associated with substantial disease burden worldwide. In each category we discuss the pathogenic roles of miRNAs in the context of their evolved functions, as well as current and potential advances in targeting these miRNAs for disease therapy.
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Affiliation(s)
- Shan Quah
- A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology, and Research (A*STAR), 8A Biomedical Grove #06-06 Immunos, Singapore 138648, Republic of Singapore
| | - Gowtham Subramanian
- A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology, and Research (A*STAR), 8A Biomedical Grove #06-06 Immunos, Singapore 138648, Republic of Singapore
| | - Jonathan S L Tan
- A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology, and Research (A*STAR), 8A Biomedical Grove #06-06 Immunos, Singapore 138648, Republic of Singapore
| | | | - Prabha Sampath
- A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology, and Research (A*STAR), 8A Biomedical Grove #06-06 Immunos, Singapore 138648, Republic of Singapore; Genome Institute of Singapore, Agency for Science, Technology, and Research, 60 Biopolis Street, #02-01 Genome, Singapore 138672, Republic of Singapore; Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Republic of Singapore; Skin Research Institute of Singapore (SRIS), 11 Mandalay Road #17-01 Clinical Sciences Building, Singapore 308232, Republic of Singapore.
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22
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Janga H, Schmerer N, Aznaourova M, Schulte LN. Non-coding RNA Networks in Infection. Methods Mol Biol 2025; 2883:53-77. [PMID: 39702704 DOI: 10.1007/978-1-0716-4290-0_3] [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] [Indexed: 12/21/2024]
Abstract
In the face of global health challenges posed by infectious diseases and the emergence of drug-resistant pathogens, the exploration of cellular non-coding RNA (ncRNA) networks has unveiled new dimensions in infection research. Particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have emerged as instrumental players in ensuring a balance between protection against hyper-inflammatory conditions and the effective elimination of pathogens. Specifically, ncRNAs, such as the miRNA miR-155 or the lncRNAs MaIL1 (macrophage interferon-regulatory lncRNA 1), and LUCAT1 (lung cancer-associated transcript 1) have been recurrently linked to infectious and inflammatory diseases. Together with other ncRNAs, discussed in this chapter, they form a complex regulatory network shaping the host response to pathogens. Additionally, some pathogens exploit these ncRNAs to establish and sustain infections, underscoring their dual roles in host protection and colonization. Despite the substantial progress made, the vast majority of ncRNA loci remains unexplored, with ongoing research likely to reveal novel ncRNA categories and expand our understanding of their roles in infections. This chapter consolidates current insights into ncRNA-mediated regulatory networks, highlighting their contributions to severe diseases and their potential as targets and biomarkers for innovative therapeutic strategies.
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Affiliation(s)
| | - Nils Schmerer
- Institute for Lung Research, Philipps University, Marburg, Germany
| | | | - Leon N Schulte
- Institute for Lung Research, Philipps University, Marburg, Germany.
- German Center for Lung Research, Giessen, Germany.
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23
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Hill M, Stapleton S, Nguyen PT, Sais D, Deutsch F, Gay VC, Marsh DJ, Tran N. The potential regulation of the miR-17-92a cluster by miR-21. Int J Biochem Cell Biol 2025; 178:106705. [PMID: 39615668 DOI: 10.1016/j.biocel.2024.106705] [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: 05/30/2024] [Revised: 10/31/2024] [Accepted: 11/26/2024] [Indexed: 12/16/2024]
Abstract
MicroRNAs (miRNA,miRs) are small noncoding RNAs that are ubiquitously expressed in all mammalian cells. Their primary function is the regulation of nascent RNA transcripts by direct binding to regions on the target. There is now exciting data to suggest that these miRNAs can bind to other miRNAs, and this may have a broader impact on gene regulation in disease states. The oncomiR miR-21 is one of the highest-expressing miRNAs in cancer cells, and in this study, we characterise which miRNAs could be potential targets of miR-21. In cancer cells delivered with a miR-21 mimic, there was an observable shift of the miRNA milieu. We demonstrate that the miR-17-92a cluster, which harbours six miRNA members, may be a target for miR-21 regulation. Additionally, the primary transcript of miR-17-92a was reduced in the presence of miR-21. In the broader context of miR:miR regulation, overexpression of miR-21 shifted the expression of more than 150 miRNAs, including those known to regulate genes in cancer pathways such as the MAPK signalling and FoxO pathways. This study expands upon our limited understanding of miR:miR regulatory network and reinforces the concept that miRNAs can regulate each other, thereby influencing broader gene networks.
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Affiliation(s)
- Meredith Hill
- School of Biomedical Engineering, Faculty of Engineering, and Information Technology, University of Technology Sydney, Australia
| | - Sarah Stapleton
- School of Biomedical Engineering, Faculty of Engineering, and Information Technology, University of Technology Sydney, Australia
| | | | - Dayna Sais
- School of Biomedical Engineering, Faculty of Engineering, and Information Technology, University of Technology Sydney, Australia
| | - Fiona Deutsch
- School of Biomedical Engineering, Faculty of Engineering, and Information Technology, University of Technology Sydney, Australia
| | - Valerie C Gay
- School of Electrical and Data Engineering, Faculty of Engineering, and Information Technology, University of Technology Sydney, Australia
| | - Deborah J Marsh
- Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia
| | - Nham Tran
- School of Biomedical Engineering, Faculty of Engineering, and Information Technology, University of Technology Sydney, Australia.
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24
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Sood S, Tiwari A, Sangwan J, Vohra M, Sinha NR, Tripathi R, Sangwan VS, Mohan RR. Role of epigenetics in corneal health and disease. Prog Retin Eye Res 2025; 104:101318. [PMID: 39547455 PMCID: PMC11710990 DOI: 10.1016/j.preteyeres.2024.101318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 11/17/2024]
Abstract
Epigenetics plays a vital role in corneal health and diseases. Epigenetic changes regulate the expression of genes by altering the accessibility of chromatin via histone modifications, DNA methylation and miRNAs without altering DNA sequence. Ocular trauma and infections are common causes of corneal damage, vision impairment, and mono/bilateral blindness worldwide. Mounting literature shows that epigenetic modifications can modulate corneal clarity, function, and pathogenesis including inflammation, wound healing, fibrosis, and neovascularization. Additionally, epigenetic modifications can be targeted to reverse corneal pathologies and develop interventional therapies. However, current understanding on how epigenetic modifications lead to corneal abnormalities and diseases is limited. This review provides in-depth knowledge and mechanistic understanding of epigenetics alterations in corneal pathogenesis, and information on potential epigenetic targets for treatment of corneal diseases.
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Affiliation(s)
- Swati Sood
- Departments of Veterinary Medicine & Surgery, College of Veterinary Medicine University of Missouri, Columbia, MO, USA
| | - Anil Tiwari
- Departments of Veterinary Medicine & Surgery, College of Veterinary Medicine University of Missouri, Columbia, MO, USA; Eicher-Shroff Centre for Stem Cells Research (ESC-SCR), Dr. Shroff Charity Eye Hospital, Delhi, India
| | - Jyoti Sangwan
- Eicher-Shroff Centre for Stem Cells Research (ESC-SCR), Dr. Shroff Charity Eye Hospital, Delhi, India
| | - Mehak Vohra
- Eicher-Shroff Centre for Stem Cells Research (ESC-SCR), Dr. Shroff Charity Eye Hospital, Delhi, India
| | - Nishant R Sinha
- Departments of Veterinary Medicine & Surgery, College of Veterinary Medicine University of Missouri, Columbia, MO, USA; Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO, USA
| | - Ratnakar Tripathi
- Departments of Veterinary Medicine & Surgery, College of Veterinary Medicine University of Missouri, Columbia, MO, USA; Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA
| | - Virender S Sangwan
- Eicher-Shroff Centre for Stem Cells Research (ESC-SCR), Dr. Shroff Charity Eye Hospital, Delhi, India
| | - Rajiv R Mohan
- Departments of Veterinary Medicine & Surgery, College of Veterinary Medicine University of Missouri, Columbia, MO, USA; Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO, USA.
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25
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Barrero-Torres DM, Herrera-Torres G, Pérez J, Martínez-Moreno Á, Martínez-Moreno FJ, Flores-Velázquez LM, Buffoni L, Rufino-Moya PJ, Ruiz-Campillo MT, Molina-Hernández V. Unraveling the microRNAs Involved in Fasciolosis: Master Regulators of the Host-Parasite Crosstalk. Int J Mol Sci 2024; 26:204. [PMID: 39796061 PMCID: PMC11719827 DOI: 10.3390/ijms26010204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/24/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
Fasciolosis is a neglected tropical disease caused by helminth parasites of the genus Fasciola spp., including Fasciola hepatica (F. hepatica) and Fasciola gigantica (F. gigantica), being a major zoonotic problem of human and animal health. Its control with antihelminthics is becoming ineffective due to the increase in parasite resistance. Developing new therapeutic protocols is crucial to a deeper knowledge of the molecular bases in the host-parasite interactions. The high-throughput omics technologies have dramatically provided unprecedented insights into the complexity of the molecular host-parasite crosstalk. MicroRNAs (miRNAs) are key players as critical regulators in numerous biological processes, modifying the gene expression of cells by degradation of messenger RNA (mRNA), regulating transcription and translation functions, protein positioning, cell cycle integrity, differentiation and apoptosis. The large-scale exploration of miRNAs, including the miRNome, has offered great scientific knowledge of steps in fasciolosis, further scrutinizing the pathogenesis, the growth and development of their strains and their interaction with the host for the survival of the different parasite stages. This review compiles the updated knowledge related to miRNAs involved in fasciolosis and the generated miRNome, highlighting the importance of these key molecules in the host-parasite interactions and the pathogenesis of Fasciola spp. directing towards the development of new biotherapeutic protocols for the control of fasciolosis.
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Affiliation(s)
- Diana María Barrero-Torres
- Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (D.M.B.-T.); (G.H.-T.); (J.P.); (L.M.F.-V.)
| | - Guillem Herrera-Torres
- Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (D.M.B.-T.); (G.H.-T.); (J.P.); (L.M.F.-V.)
| | - José Pérez
- Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (D.M.B.-T.); (G.H.-T.); (J.P.); (L.M.F.-V.)
| | - Álvaro Martínez-Moreno
- Departamento de Sanidad Animal (Área de Parasitología), UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (Á.M.-M.); (F.J.M.-M.); (L.B.); (P.J.R.-M.)
| | - Francisco Javier Martínez-Moreno
- Departamento de Sanidad Animal (Área de Parasitología), UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (Á.M.-M.); (F.J.M.-M.); (L.B.); (P.J.R.-M.)
| | - Luis Miguel Flores-Velázquez
- Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (D.M.B.-T.); (G.H.-T.); (J.P.); (L.M.F.-V.)
- Unidad de Anatomía, Histología y Patología Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias Naturales, Universidad San Sebastián, Campus Puerto Montt, Puerto Montt 5480000, Chile
| | - Leandro Buffoni
- Departamento de Sanidad Animal (Área de Parasitología), UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (Á.M.-M.); (F.J.M.-M.); (L.B.); (P.J.R.-M.)
| | - Pablo José Rufino-Moya
- Departamento de Sanidad Animal (Área de Parasitología), UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (Á.M.-M.); (F.J.M.-M.); (L.B.); (P.J.R.-M.)
| | - María Teresa Ruiz-Campillo
- Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (D.M.B.-T.); (G.H.-T.); (J.P.); (L.M.F.-V.)
| | - Verónica Molina-Hernández
- Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, 14071 Córdoba, Spain; (D.M.B.-T.); (G.H.-T.); (J.P.); (L.M.F.-V.)
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26
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Zhang Y, Li Y, Han H, Wang X, Gao S, Zhao Q, Bieerdebieke H, Xu L, Zang Q, Wang H, Bai P, Lin K. Identification of miRNAs Involved in Olfactory Regulation in Antennae of Beet Webworm, Loxostege sticticalis (Lepidoptera: Pyralidae). Life (Basel) 2024; 14:1705. [PMID: 39768411 PMCID: PMC11677245 DOI: 10.3390/life14121705] [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: 11/12/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025] Open
Abstract
The beet webworm, Loxostege sticticalis, is a typical migratory pest. Although miRNAs participate in many physiological functions, little is known about the functions of miRNAs in olfactory regulation. In this study, 1120 (869 known and 251 novel) miRNAs were identified in the antennae of L. sticticalis by using high-throughput sequencing technology. Among the known miRNAs, 189 from 49 families were insect-specific, indicating that these miRNAs might play unique roles in insects. Furthermore, based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found that 3647 and 1393 miRNAs were associated with localization and the regulation of localization, respectively, and 80 miRNAs were enriched in the neuroactive ligand-receptor interaction pathway. These miRNAs might be involved in the olfactory system of L. sticticalis. Notably, qRT-PCR showed that most of the tested miRNAs presented similar expression patterns compared with the RNA-seq data and that miR-87-3, novel-miR-78, and novel-miR-142 were significantly differentially expressed in the antennae of males and females. In addition, 21 miRNAs were predicted to target 23 olfactory genes, including 10 odorant-binding proteins (OBPs), 3 chemosensory proteins (CSPs), 4 odorant receptors (ORs), 1 ionotropic receptor (IR), and 5 gustatory receptors (GRs). The olfactory-related miRNAs exhibited low-abundance transcripts, except undef-miR-55 and undef-miR-523, and gender-biased expression was not observed for olfactory-related miRNAs. Our findings provide an overview of the potential miRNAs involved in olfactory regulation, which may provide important information on the function of miRNAs in the insect olfactory system.
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Affiliation(s)
- Yu Zhang
- Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China; (Y.Z.); (S.G.); (Q.Z.); (L.X.); (H.W.)
| | - Yanyan Li
- Research Center for Grassland Entomology, Inner Mongolia Agricultural University, Hohhot 010020, China; (Y.L.); (H.H.)
| | - Haibin Han
- Research Center for Grassland Entomology, Inner Mongolia Agricultural University, Hohhot 010020, China; (Y.L.); (H.H.)
| | - Xiaoling Wang
- Xilin Gol League Agricultural and Animal Husbandry Technology Promotion Center, Xilinhot 026000, China;
| | - Shujing Gao
- Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China; (Y.Z.); (S.G.); (Q.Z.); (L.X.); (H.W.)
| | - Qing Zhao
- Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China; (Y.Z.); (S.G.); (Q.Z.); (L.X.); (H.W.)
| | - Halima Bieerdebieke
- The Center for Grassland Biological Disaster Prevention of Xinjiang Uygur Autonomous Region, Urumqi 830049, China;
| | - Linbo Xu
- Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China; (Y.Z.); (S.G.); (Q.Z.); (L.X.); (H.W.)
| | - Qicong Zang
- Heilongjiang Province Grassland Station, Harbin 150069, China;
| | - Hui Wang
- Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China; (Y.Z.); (S.G.); (Q.Z.); (L.X.); (H.W.)
| | - Penghua Bai
- Institute of Plant Protection, Tianjin Academy of Agricultural Sciences, Tianjin 300384, China
| | - Kejian Lin
- Key Laboratory of Biohazard Monitoring, Green Prevention and Control for Artificial Grassland, Ministry of Agriculture and Rural Affairs, Institute of Grassland Research of Chinese Academy of Agricultural Sciences, Hohhot 010010, China; (Y.Z.); (S.G.); (Q.Z.); (L.X.); (H.W.)
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27
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Wang Z, Wang PS, Yang C. Dysregulation of Long Non-coding RNAs-the Novel lnc in Metal Toxicity and Carcinogenesis. Curr Environ Health Rep 2024; 12:3. [PMID: 39715843 PMCID: PMC11755759 DOI: 10.1007/s40572-024-00468-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2024] [Indexed: 12/25/2024]
Abstract
PURPOSE OF REVIEW Metals are common environmental pollutants. Acute and chronic exposures to non-essential toxic metals or excessive essential metals cause various diseases including cancer in humans. However, the underlying mechanisms have not been well understood. Long non-coding RNAs (lncRNAs) refer to RNA transcripts that have more than 200 nucleotides but do not have significant protein coding capacities. While lncRNAs were once considered transcription noise, they have become increasingly recognized as crucial players in various physiological and pathogenesis processes. The goal of this article is to review and discuss recent studies that show important roles of lncRNA dysregulations in metal toxicity and carcinogenesis. RECENT FINDINGS Recent studies showed that metal exposures dysregulate expression of lncRNAs in cultured cells, animals and humas. However, only a few studies determined the mechanisms of how metal exposure dysregulated expression of lncRNAs. The majority of the studies reported the association of abnormally expressed lncRNAs with various toxic effects of metal exposures, only limited studies established causal relationships demonstrating causal roles of dysregulated lncRNAs in metal toxicity and carcinogenesis. Mechanistically, most studies reported that dysregulated lncRNAs functioned as microRNA sponges to regulate gene expression, much less studies explored other mechanisms of lncRNA actions. It is evident that metal exposures dysregulate expression of lncRNAs, which may serve as novel mediators in metal toxicity and carcinogenesis. Further studies are needed to establish dysregulated lncRNAs as potential diagnostic biomarkers and therapeutic targets for metal exposure-associated diseases.
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Affiliation(s)
- Zhishan Wang
- Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, 11794, USA
- Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, 101 Nicolls Road, Stony Brook, NY, 11794, USA
| | - Po-Shun Wang
- Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, 11794, USA
| | - Chengfeng Yang
- Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, 11794, USA.
- Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, 101 Nicolls Road, Stony Brook, NY, 11794, USA.
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28
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Hall I, O'Steen M, Gold S, C Keane S, Weidmann CA. Template switching enables chemical probing of native RNA structures. RNA (NEW YORK, N.Y.) 2024; 31:113-125. [PMID: 39438135 DOI: 10.1261/rna.079926.123] [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: 12/13/2023] [Accepted: 09/26/2024] [Indexed: 10/25/2024]
Abstract
RNAs are often studied in nonnative sequence contexts to facilitate structural studies. However, seemingly innocuous changes to an RNA sequence may perturb the native structure and generate inaccurate or ambiguous structural models. To facilitate the investigation of native RNA secondary structure by selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), we engineered an approach that couples minimal enzymatic steps to RNA chemical probing and mutational profiling (MaP) reverse transcription (RT) methods-a process we call template switching and mutational profiling (Switch-MaP). In Switch-MaP, RT templates and additional library sequences are added postprobing through ligation and template switching, capturing reactivities for every nucleotide. For a candidate SAM-I riboswitch, we compared RNA structure models generated by the Switch-MaP approach to those of traditional primer-based MaP, including RNAs with or without appended structure cassettes. Primer-based MaP masked reactivity data in the 5' and 3' ends of the RNA, producing ambiguous ensembles inconsistent with the conserved SAM-I riboswitch secondary structure. Structure cassettes enabled unambiguous modeling of an aptamer-only construct but introduced nonnative interactions in the full-length riboswitch. In contrast, Switch-MaP provided reactivity data for all nucleotides in each RNA and enabled unambiguous modeling of secondary structure, consistent with the conserved SAM-I fold. Switch-MaP is a straightforward alternative approach to primer-based and cassette-based chemical probing methods that precludes primer masking and the formation of alternative secondary structures due to nonnative sequence elements.
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Affiliation(s)
- Ian Hall
- Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
| | - Martin O'Steen
- Program in Biophysics, University of Michigan, Ann Arbor, Michigan 48109, USA
| | - Sophie Gold
- Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
| | - Sarah C Keane
- Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
- Program in Biophysics, University of Michigan, Ann Arbor, Michigan 48109, USA
| | - Chase A Weidmann
- Department of Biological Chemistry, Center for RNA Biomedicine, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
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Li X, Qin W, Wang W, Liu W, Dong T, Liu A, Cai H, Xu Z, Zeng J. Screening and Studying of Blood miRNAs as Potential Diagnostic Markers for Papillary Thyroid Carcinoma. Onco Targets Ther 2024; 17:1173-1185. [PMID: 39678015 PMCID: PMC11645959 DOI: 10.2147/ott.s489559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 12/03/2024] [Indexed: 12/17/2024] Open
Abstract
Objective MiRNAs play a pivotal role in tumorigenesis and development by exerting negative regulation on the expression of target genes. In this study, bioinformatics techniques and online database were employed to investigate the specific miRNA-target gene regulatory network in PTC, which was subsequently validated using human blood samples and compared to existing tumor markers. Methods The miRNA (GSE50901) and Gene Expression (GSE113629) chip screening data of human PTC tissues were retrieved from GEO database. A comparative analysis was conducted using the GEO2R to identify differentially expressed miRNAs and target genes of the patients with PTC. Prediction of the miRNA-target gene regulatory network, related signal transduction pathways, biological effects and their relationship to prognosis was performed based on GO, KEGG, qRT-PCR detection of human blood samples, analysis of correlation on the existing pathological tumor markers, and ROC. Results Compared to the corresponding normal thyroid tissues, a total of 2116 miRNAs were found to be differentially expressed in PTC patients, including 1968 up-regulated and 148 down-regulated genes. The abnormally expressed genes primarily participated in signal pathways associated with tumorigenesis and abnormal gene transcription. By utilizing data from the GEO database, five miRNAs closely linked to PTC prognosis were identified, which were miR-221-3p, miR-222-3p, miR-182-5p, miR-135a-5p, and miR-34a-5p, with elucidating the target genes. Experimental validation, correlation analysis with tumor markers along with bioinformatics analysis revealed a significant increase in expression levels of miR-182-5p in PTC patients which positively correlated with poor prognosis. These molecules could play crucial roles in both initiation and progression of PTC. Conclusion This study identified potential novel blood-based miRNA biomarkers for PTC through bioinformatics analysis combined with the detection of human blood samples, thereby offering new possibilities for significant biomarkers associated with diagnosis and prognosis of PTC.
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Affiliation(s)
- Xize Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China
| | - Wen Qin
- The Hospital Wing, Shandong University, Jinan, 250012, People’s Republic of China
| | - Wenting Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China
| | - Weilin Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China
| | - Tianyi Dong
- Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China
| | - Aixiang Liu
- Department of Clinical Laboratory, Zaozhuang Municipal Hospital, Zaozhuang, 277102, People’s Republic of China
| | - Haojie Cai
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China
| | - Zhouhan Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China
| | - Jiping Zeng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Jinan, 250012, People’s Republic of China
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266113, People’s Republic of China
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Drula R, Calin GA. MicroRNAs: where brilliance, perseverance, and ambition converged. J Clin Invest 2024; 135:e189625. [PMID: 39656547 PMCID: PMC11735086 DOI: 10.1172/jci189625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2025] Open
Affiliation(s)
- Rares Drula
- Translational Molecular Pathology Department
| | - George A. Calin
- Translational Molecular Pathology Department
- Leukemia Department, and
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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31
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Li W, Yu L. Role and therapeutic perspectives of extracellular vesicles derived from liver and adipose tissue in metabolic dysfunction-associated steatotic liver disease. ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 2024; 52:355-369. [PMID: 38833340 DOI: 10.1080/21691401.2024.2360008] [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: 10/13/2023] [Accepted: 05/22/2024] [Indexed: 06/06/2024]
Abstract
The global epidemic of metabolic diseases has led to the emergence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), which pose a significant threat to human health. Despite recent advances in research on the pathogenesis and treatment of MASLD/MASH, there is still a lack of more effective and targeted therapies. Extracellular vesicles (EVs) discovered in a wide range of tissues and body fluids encapsulate different activated biomolecules and mediate intercellular communication. Recent studies have shown that EVs derived from the liver and adipose tissue (AT) play vital roles in MASLD/MASH pathogenesis and therapeutics, depending on their sources and intervention types. Besides, adipose-derived stem cell (ADSC)-derived EVs appear to be more effective in mitigating MASLD/MASH. This review presents an overview of the definition, extraction strategies, and characterisation of EVs, with a particular focus on the biogenesis and release of exosomes. It also reviews the effects and potential molecular mechanisms of liver- and AT-derived EVs on MASLD/MASH, and emphasises the contribution and clinical therapeutic potential of ADSC-derived EVs. Furthermore, the future perspective of EV therapy in a clinical setting is discussed.
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Affiliation(s)
- Wandi Li
- Senior Department of Burns and Plastic Surgery, the Fourth Medical Center of PLA General Hospital, Haidian District, Beijing, P.R. China
| | - Lili Yu
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, P.R. China
- Endocrine Department, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Henan, P.R. China
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Xiang W, Yang F, Pu X, Zhao S, Wang P. A New Perspective on Pig Genetics and Breeding: microRNA. Reprod Domest Anim 2024; 59:e14751. [PMID: 39639849 DOI: 10.1111/rda.14751] [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: 07/21/2024] [Revised: 11/05/2024] [Accepted: 11/17/2024] [Indexed: 12/07/2024]
Abstract
microRNA (miRNA) is a class of small non-coding RNA molecules that are widely expressed in organisms and play an important role in the regulation of gene expression at the post-transcriptional level. In recent years, researchers have begun to explore its effects on the development of domestic animals and have begun to think about its potential role in modern molecular breeding. Increasing evidence shows that miRNA play a central role in the regulation of pig fertility, pork product quality and disease resistance. Understanding the physiological mechanism of miRNA will be able to better guide future breeding work. In this paper, we will review the research progress of the function and mechanism of miRNA in combination with the above economic characteristics of pigs. The reported miRNA and their target genes were sorted out to evaluate their potential role in improving economic traits such as pig fertility, meat quality and disease resistance, to provide a reference for modern pig molecular breeding.
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Affiliation(s)
- Wei Xiang
- School of Advanced Agriculture and Bioengineering, Yangtze Normal University, Chongqing, China
| | - Fan Yang
- College of Bioengineering, Chongqing University, Chongqing, China
| | - Xiufen Pu
- College of Bioengineering, Chongqing University, Chongqing, China
| | - Shuang Zhao
- College of Bioengineering, Chongqing University, Chongqing, China
| | - Pingqing Wang
- College of Bioengineering, Chongqing University, Chongqing, China
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Rykalo N, Riehl L, Kress M. The gut microbiome and the brain. Curr Opin Support Palliat Care 2024; 18:282-291. [PMID: 39250732 DOI: 10.1097/spc.0000000000000717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
PURPOSE OF REVIEW The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions. RECENT FINDINGS The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function. SUMMARY Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions.
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Affiliation(s)
- Nadiia Rykalo
- Department of Physiology and Medical Physics, Institute of Physiology, Medical University Innsbruck, Austria
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Elazab IM, El-Feky OA, Khedr EG, El-Ashmawy NE. Prostate cancer and the cell cycle: Focusing on the role of microRNAs. Gene 2024; 928:148785. [PMID: 39053658 DOI: 10.1016/j.gene.2024.148785] [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: 03/25/2024] [Revised: 07/12/2024] [Accepted: 07/18/2024] [Indexed: 07/27/2024]
Abstract
Prostate cancer is the most frequent solid tumor in terms of incidence and ranks second only to lung cancer in terms of cancer mortality among men. It has a considerably high mortality rate; around 375,000 deaths occurred worldwide in 2020. In 2024, the American Cancer Society estimated that the number of new prostate cancer cases will be around 299,010 cases, and the estimated deaths will be around 32,250 deaths only in the USA. Cell cycle dysregulation is inevitable in cancer etiology and is targeted by various therapies in cancer treatment. MicroRNAs (miRNAs) are small, endogenous, non-coding regulatory molecules involved in both normal and abnormal cellular events. One of the cellular processes regulated by miRNAs is the cell cycle. Although there are some exceptions, tumor suppressor miRNAs could potentially arrest the cell cycle by downregulating several molecular machineries involved in catalyzing the cell cycle progression. In contrast, oncogenic miRNAs (oncomirs) help the cell cycle to progress by targeting various regulatory proteins such as retinoblastoma (Rb) or cell cycle inhibitors such as p21 or p27, and hence may contribute to prostate cancer progression; however, this is not always the case. In this review, we emphasize how a dysregulated miRNA expression profile is linked to an abnormal cell cycle progression in prostate cancer, which subsequently paves the way to a new therapeutic option for prostate cancer.
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Affiliation(s)
- Ibrahim M Elazab
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Al-Geish Street, Tanta, El-Gharbia, 31527, Egypt.
| | - Ola A El-Feky
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Al-Geish Street, Tanta, El-Gharbia, 31527, Egypt.
| | - Eman G Khedr
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Al-Geish Street, Tanta, El-Gharbia, 31527, Egypt.
| | - Nahla E El-Ashmawy
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Al-Geish Street, Tanta, El-Gharbia, 31527, Egypt; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, BUE, Cairo, 11837, Egypt.
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Niazi SK, Magoola M. MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products-A Prospective Analysis. Int J Mol Sci 2024; 25:12883. [PMID: 39684593 PMCID: PMC11641023 DOI: 10.3390/ijms252312883] [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: 10/21/2024] [Revised: 11/20/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
MicroRNAs (miRNAs) maintain cellular homeostasis by blocking mRNAs by binding with them to fine-tune the expression of genes across numerous biological pathways. The 2024 Nobel Prize in Medicine and Physiology for discovering miRNAs was long overdue. We anticipate a deluge of research work involving miRNAs to repeat the history of prizes awarded for research on other RNAs. Although miRNA therapies are included for several complex diseases, the realization that miRNAs regulate genes and their roles in addressing therapies for hundreds of diseases are expected; but with advancement in drug discovery tools, we anticipate even faster entry of new drugs. To promote this, we provide details of the current science, logic, intellectual property, formulations, and regulatory process with anticipation that many more researchers will introduce novel therapies based on the discussion and advice provided in this paper.
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Chen LL, Kim VN. Small and long non-coding RNAs: Past, present, and future. Cell 2024; 187:6451-6485. [PMID: 39547208 DOI: 10.1016/j.cell.2024.10.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 10/13/2024] [Accepted: 10/15/2024] [Indexed: 11/17/2024]
Abstract
Since the introduction of the central dogma of molecular biology in 1958, various RNA species have been discovered. Messenger RNAs transmit genetic instructions from DNA to make proteins, a process facilitated by housekeeping non-coding RNAs (ncRNAs) such as small nuclear RNAs (snRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). Over the past four decades, a wide array of regulatory ncRNAs have emerged as crucial players in gene regulation. In celebration of Cell's 50th anniversary, this Review explores our current understanding of the most extensively studied regulatory ncRNAs-small RNAs and long non-coding RNAs (lncRNAs)-which have profoundly shaped the field of RNA biology and beyond. While small RNA pathways have been well documented with clearly defined mechanisms, lncRNAs exhibit a greater diversity of mechanisms, many of which remain unknown. This Review covers pivotal events in their discovery, biogenesis pathways, evolutionary traits, action mechanisms, functions, and crosstalks among ncRNAs. We also highlight their roles in pathophysiological contexts and propose future research directions to decipher the unknowns of lncRNAs by leveraging lessons from small RNAs.
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Affiliation(s)
- Ling-Ling Chen
- Key Laboratory of RNA Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; New Cornerstone Science Laboratory, Shenzhen, China.
| | - V Narry Kim
- Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
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Feng N, Mandal A, Jambhale A, Narnur P, Chen G, Akula N, Kramer R, Kolachana B, Xu Q, McMahon FJ, Lipska BK, Auluck PK, Marenco S. Schizophrenia risk-associated SNPs affect expression of microRNA 137 host gene: a postmortem study. Hum Mol Genet 2024; 33:1939-1947. [PMID: 39239979 DOI: 10.1093/hmg/ddae130] [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: 03/14/2024] [Revised: 08/23/2024] [Accepted: 08/28/2024] [Indexed: 09/07/2024] Open
Abstract
Common variants in the MicroRNA 137 host gene MIR137HG and its adjacent gene DPYD have been associated with schizophrenia risk and the latest Psychiatric Genomics Consortium (PGC). Genome-Wide Association Study on schizophrenia has confirmed and extended these findings. To elucidate the association of schizophrenia risk-associated SNPs in this genomic region, we examined the expression of both mature and immature transcripts of the miR-137 host gene (MIR137HG) in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of postmortem brain samples of donors with schizophrenia and psychiatrically-unaffected controls using qPCR and RNA-Seq approaches. No differential expression of miR-137, MIR137HG, or its transcripts was observed. Two schizophrenia risk-associated SNPs identified in the PGC study, rs11165917 (DLPFC: P = 2.0e-16; sgACC: P = 6.4e-10) and rs4274102 (DLPFC: P = 0.036; sgACC: P = 0.002), were associated with expression of the MIR137HG long non-coding RNA transcript MIR137HG-203 (ENST00000602672.2) in individuals of European ancestry. Carriers of the minor (risk) allele of rs11165917 had significantly lower expression of MIR137HG-203 compared with those carrying the major allele. However, we were unable to validate this result by short-read sequencing of RNA extracted from DLPFC or sgACC tissue. This finding suggests that immature transcripts of MIR137HG may contribute to genetic risk for schizophrenia.
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Affiliation(s)
- Ningping Feng
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Ajeet Mandal
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Ananya Jambhale
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Pranav Narnur
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Gang Chen
- Scientific and Statistical Computing Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, bldg 10, room 1D73, Bethesda, MD 20892, United States
| | - Nirmala Akula
- Human Genetics Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 35 Convent Dr. Bldg. 35, RM 1A202, MSC 3719, Bethesda, MD 20892, United States
| | - Robin Kramer
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Bhaskar Kolachana
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Qing Xu
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Francis J McMahon
- Human Genetics Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 35 Convent Dr. Bldg. 35, RM 1A202, MSC 3719, Bethesda, MD 20892, United States
| | - Barbara K Lipska
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Pavan K Auluck
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
| | - Stefano Marenco
- Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States
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Sarapata K, Kania A. Revealing miRNAs patterns by employing matrix representations and energy analysis. J Mol Graph Model 2024; 132:108835. [PMID: 39106629 DOI: 10.1016/j.jmgm.2024.108835] [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: 06/24/2023] [Revised: 07/16/2024] [Accepted: 07/29/2024] [Indexed: 08/09/2024]
Abstract
MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression. Despite their relatively short length (about 21 nucleotides), they can regulate thousands of transcripts within a cell. Due to their low complementarity to targets, studying their activity and binding region preferences (3'UTR, 5'UTR, or CDS) is challenging. In this paper, we analyzed a set of human miRNAs to uncover their general patterns. We began with a sequence logo to verify conservation at specific positions. To discover long-range correlations, we employed chaos game representation (CGR) and genomatrix, methods that enable both graphical and analytical analysis of sequence sets and are well-established in bioinformatics. Our results showed that miRNAs exhibit strongly non-random and characteristic patterns. To incorporate physicochemical properties into the analysis, we applied the electron-ion interaction potential (EIIP) parameter. An important part of our study was to validate the division of miRNAs into two parts-seed and puzzle. The seed region is responsible for target binding, while the puzzle region likely interacts with the RISC complex. We estimated duplex binding energy within the 3'UTR, 5'UTR, and CDS regions using the miRanda tool. Based on the median energy distribution, we divided the miRNAs into two subsets, reflecting different patterns in chaos game representation. Interestingly, one subset displayed significant similarity to conserved and highly confidential miRNAs. Our results confirm the low complementarity of miRNA/mRNA interactions and support the functional division of miRNA structure. Additionally, we present findings related to the localization of transcript target sites, which form the basis for further analyses.
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Affiliation(s)
- Krzysztof Sarapata
- Department of Computational Biophysics and Bioinformatics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland
| | - Adrian Kania
- Department of Computational Biophysics and Bioinformatics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland.
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Bi F, Gao C, Guo H. Epigenetic regulation of cardiovascular diseases induced by behavioral and environmental risk factors: Mechanistic, diagnostic, and therapeutic insights. FASEB Bioadv 2024; 6:477-502. [PMID: 39512842 PMCID: PMC11539034 DOI: 10.1096/fba.2024-00080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/30/2024] [Accepted: 09/05/2024] [Indexed: 11/15/2024] Open
Abstract
Behavioral and environmental risk factors are critical in the development and progression of cardiovascular disease (CVD). Understanding the molecular mechanisms underlying these risk factors will offer valuable insights for targeted preventive and therapeutic strategies. Epigenetic modifications, including DNA methylation, histone modifications, chromatin remodeling, noncoding RNA (ncRNA) expression, and epitranscriptomic modifications, have emerged as key mediators connecting behavioral and environmental risk factors to CVD risk and progression. These epigenetic alterations can profoundly impact on cardiovascular health and susceptibility to CVD by influencing cellular processes, development, and disease risk over an individual's lifetime and potentially across generations. This review examines how behavioral and environmental risk factors affect CVD risk and health outcomes through epigenetic regulation. We review the epigenetic effects of major behavioral risk factors (such as smoking, alcohol consumption, physical inactivity, unhealthy diet, and obesity) and environmental risk factors (including air and noise pollution) in the context of CVD pathogenesis. Additionally, we explore epigenetic biomarkers, considering their role as causal or surrogate indicators, and discuss epigenetic therapeutics targeting the mechanisms through which these risk factors contribute to CVD. We also address future research directions and challenges in leveraging epigenetic insights to reduce the burden of CVD related to behavioral and environmental factors and improve public health outcomes. This review aims to provide a comprehensive understanding of behavioral and environmental epigenetics in CVD and offer valuable strategies for therapeutic intervention.
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Affiliation(s)
- Feifei Bi
- Nora Eccles Harrison Cardiovascular Research and Training Institute, University of UtahSalt Lake CityUtahUSA
- Division of Cardiothoracic Surgery, Department of SurgerySchool of Medicine, University of UtahSalt Lake CityUtahUSA
| | - Chen Gao
- Department of Pharmacology and Systems PhysiologyUniversity of CincinnatiCincinnatiOhioUSA
| | - Hongchao Guo
- Nora Eccles Harrison Cardiovascular Research and Training Institute, University of UtahSalt Lake CityUtahUSA
- Division of Cardiothoracic Surgery, Department of SurgerySchool of Medicine, University of UtahSalt Lake CityUtahUSA
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Kim YK, Han J. Nobel-winning microRNA, the micromaestro of gene silencing. Mol Cells 2024; 47:100123. [PMID: 39414082 PMCID: PMC11532464 DOI: 10.1016/j.mocell.2024.100123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 10/10/2024] [Indexed: 10/18/2024] Open
Affiliation(s)
- Young-Kook Kim
- Department of Biochemistry, Chonnam National University Medical School, Jeollanam-do 58128, Republic of Korea.
| | - Jinju Han
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
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Jia L, Meng Q, Xu X. Autophagy-related miRNAs, exosomal miRNAs, and circRNAs in tumor progression and drug-and radiation resistance in colorectal cancer. Pathol Res Pract 2024; 263:155597. [PMID: 39426141 DOI: 10.1016/j.prp.2024.155597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 07/16/2024] [Accepted: 09/20/2024] [Indexed: 10/21/2024]
Abstract
Targeted therapies are often more tolerable than traditional cytotoxic ones. Nurses play a critical role in providing patients and caregivers with information about the disease, available therapies, and the kind, severity, and identification of any potential adverse events. By doing this, it may be possible to ensure that any adverse effects are managed quickly, maximizing the therapeutic benefit. In colorectal cancer (CRC), autophagy-related activities are significantly influenced by miRNAs and exosomal miRNAs. CRC development and treatment resistance have been associated with the cellular process of autophagy. miRNAs, which are short non-coding RNA molecules, have the ability to control the expression of genes by binding to the 3' untranslated region (UTR) of target mRNAs and either preventing or suppressing translation. It has been discovered that several miRNAs are significant regulators of CRC autophagy. By preventing autophagy, these miRNAs enhance the survival and growth of cancer cells. Exosomes are small membrane vesicles that are released by cells and include miRNAs among other bioactive compounds. Exosomes have the ability to modify recipient cells' biological processes by delivering their cargo, which includes miRNAs. It has been demonstrated that exosomal miRNAs control autophagy in CRC in both autocrine and paracrine ways. We will discuss the potential roles of miRNAs, exosomal miRNAs, and circRNAs in CRC autophagy processes and how nursing care can reduce unfavorable outcomes.
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Affiliation(s)
- Liting Jia
- Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing 102413, China
| | - Qingyun Meng
- Gastroenterology Department, Qingdao Municipal Hospital, Qingdao 266000, China
| | - Xiaofeng Xu
- Thoracic Surgery, Qingdao Municipal Hospital, Qingdao 266000, China.
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Wightman B. It's about time: the heterochronic background for the 2024 Nobel Prize in Physiology or Medicine. Dis Model Mech 2024; 17:dmm052187. [PMID: 39601149 PMCID: PMC11625885 DOI: 10.1242/dmm.052187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024] Open
Abstract
The 2024 Nobel Prize in Physiology or Medicine has been awarded to Victor Ambros and Gary Ruvkun "for the discovery of microRNA and its role in post-transcriptional gene regulation". The award celebrates the discovery of small regulatory miRNAs and their mRNA targets, published over three decades ago. The groundwork for this discovery was laid during the early 1980s, when Ambros began studying mutations that caused heterochronic defects in the nematode Caenorhabditis elegans - or shifts in the temporal identities of cells. A major impetus to study the heterochronic genes of C. elegans was to gain mechanistic understanding of how developmental stages are specified - a fascinating question in basic and evolutionary biology. Asking fundamental biological questions with no immediate application to human health ultimately led to the discovery of a new type of RNA, which had broad implications for understanding and treating human disease.
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Affiliation(s)
- Bruce Wightman
- Biology Department, Muhlenberg College, Allentown, PA 18104, USA
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43
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Luo X, Shi J, Wang S, Jin X. The role of circular RNA targeting IGF2BPs in cancer-a potential target for cancer therapy. J Mol Med (Berl) 2024; 102:1297-1314. [PMID: 39287635 DOI: 10.1007/s00109-024-02488-8] [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: 04/07/2024] [Revised: 07/01/2024] [Accepted: 09/10/2024] [Indexed: 09/19/2024]
Abstract
Circular RNAs (circRNAs) are an interesting class of conserved single-stranded RNA molecules derived from exon or intron sequences produced by the reverse splicing of precursor mRNA. CircRNAs play important roles as microRNA sponges, gene splicing and transcriptional regulators, RNA-binding protein sponges, and protein/peptide translation factors. Abnormal functions of circRNAs and RBPs in tumor progression have been widely reported. Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) are a highly conserved family of RBPs identified in humans that function as post-transcriptional fine-tuners of target transcripts. Emerging evidence suggests that IGF2BPs regulate the processing and metabolism of RNA, including its stability, translation, and localization, and participate in a variety of cellular functions and pathophysiology. In this review, we have summarized the roles and molecular mechanisms of circRNAs and IGF2BPs in cancer development and progression. In addition, we briefly introduce the role of other RNAs and IGF2BPs in cancer, discuss the current clinical applications and challenges faced by circRNAs and IGF2BPs, and propose future directions for this promising research field.
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Affiliation(s)
- Xia Luo
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China
| | - Jiaxin Shi
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China
| | - Siyuan Wang
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China
| | - Xiaofeng Jin
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China.
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44
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Pasculli E, Gadaleta RM, Arconzo M, Cariello M, Moschetta A. The Role of Exogenous microRNAs on Human Health: The Plant-Human Trans-Kingdom Hypothesis. Nutrients 2024; 16:3658. [PMID: 39519491 PMCID: PMC11547593 DOI: 10.3390/nu16213658] [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: 10/10/2024] [Revised: 10/25/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
MicroRNAs (miRNAs) are small, endogenous, single-stranded RNAs that act on gene silencing at the post-transcriptional level by binding to a target messenger RNA (mRNA), leading to its degradation or inhibiting translation into functional proteins. The key role of miRNAs in development, proliferation, differentiation andapoptosis has been deeply investigated, revealing that deregulation in their expression is critical in various diseases, such as metabolic disorders and cancer. Since these small molecules initially evolved as a mechanism of protection against viruses and transposable elements, the fascinating hypothesis that they can move between organisms both of the same or different species has been postulated. Trans-kingdom is the term used to define the migration that occurs between species. This mechanism has been well analyzed between plants and their pests, in order to boost defense and increase pathogenicity, respectively. Intriguingly, in the last decades, the plant-human trans-kingdom migration via food intake hypothesis arose. In particular, various studies highlighted the ability of exogenous miRNAs, abundant in the mainly consumed plant-derived food, to enter the human body affecting gene expression. Notably, plant miRNAs can resist the strict conditions of the gastrointestinal tract through a methylation step that occurs during miRNA maturation, conferring high stability to these small molecules. Recent studies observed the anti-tumoral, immune modulator and anti-inflammatory abilities of trans-kingdom interaction between plant and human. Here, we depict the existing knowledge and discuss the fascinating plant-human trans-kingdom interaction, highlighting first the eventual role of plant miRNAs from foods on our somatic gene identity card and then the potential impact of using plant miRNAs as novel therapeutic avenues.
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Affiliation(s)
- Emanuela Pasculli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.P.); (R.M.G.); (M.A.)
| | - Raffaella Maria Gadaleta
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.P.); (R.M.G.); (M.A.)
- INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie d’Oro 305, 00136 Rome, Italy
| | - Maria Arconzo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.P.); (R.M.G.); (M.A.)
| | - Marica Cariello
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.P.); (R.M.G.); (M.A.)
- INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie d’Oro 305, 00136 Rome, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (E.P.); (R.M.G.); (M.A.)
- INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie d’Oro 305, 00136 Rome, Italy
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45
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Cheng XC, Tong WZ, Rui W, Feng Z, Shuai H, Zhe W. Single-cell sequencing technology in skin wound healing. BURNS & TRAUMA 2024; 12:tkae043. [PMID: 39445224 PMCID: PMC11497848 DOI: 10.1093/burnst/tkae043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 10/25/2024]
Abstract
Skin wound healing is a complicated biological process that mainly occurs in response to injury, burns, or diabetic ulcers. It can also be triggered by other conditions such as dermatitis and melanoma-induced skin cancer. Delayed healing or non-healing after skin injury presents an important clinical issue; therefore, further explorations into the occurrence and development of wound healing at the cellular and molecular levels are necessary. Single-cell sequencing (SCS) is used to sequence and analyze the genetic messages of a single cell. Furthermore, SCS can accurately detect cell expression and gene sequences. The use of SCS technology has resulted in the emergence of new concepts pertaining to wound healing, making it an important tool for studying the relevant mechanisms and developing treatment strategies. This article discusses the application value of SCS technology, the effects of the latest research on skin wound healing, and the value of SCS technology in clinical applications. Using SCS to determine potential biomarkers for wound repair will serve to accelerate wound healing, reduce scar formation, optimize drug delivery, and facilitate personalized treatments.
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Affiliation(s)
- Xu Cheng Cheng
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, No. 36 Sanhao Street, Shenyang 110004, China
| | - Wang Zi Tong
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, No. 36 Sanhao Street, Shenyang 110004, China
| | - Wang Rui
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, No. 36 Sanhao Street, Shenyang 110004, China
| | - Zhao Feng
- Department of Stem Cells and Regenerative Medicine, China Medical University, No. 77 Puhe Road, Shenyang 110013, China
| | - Hou Shuai
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, No. 36 Sanhao Street, Shenyang 110004, China
| | - Wang Zhe
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, No. 36 Sanhao Street, Shenyang 110004, China
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46
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Ritter A, Han J, Bianconi S, Henrich D, Marzi I, Leppik L, Weber B. The Ambivalent Role of miRNA-21 in Trauma and Acute Organ Injury. Int J Mol Sci 2024; 25:11282. [PMID: 39457065 PMCID: PMC11508407 DOI: 10.3390/ijms252011282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/14/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
Since their initial recognition, miRNAs have been the subject of rising scientific interest. Especially in recent years, miRNAs have been recognized to play an important role in the mediation of various diseases, and further, their potential as biomarkers was recognized. Rising attention has also been given to miRNA-21, which has proven to play an ambivalent role as a biomarker. Responding to the demand for biomarkers in the trauma field, the present review summarizes the contrary roles of miRNA-21 in acute organ damage after trauma with a specific focus on the role of miRNA-21 in traumatic brain injury, spinal cord injury, cardiac damage, lung injury, and bone injury. This review is based on a PubMed literature search including the terms "miRNA-21" and "trauma", "miRNA-21" and "severe injury", and "miRNA-21" and "acute lung respiratory distress syndrome". The present summary makes it clear that miRNA-21 has both beneficial and detrimental effects in various acute organ injuries, which precludes its utility as a biomarker but makes it intriguing for mechanistic investigations in the trauma field.
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Affiliation(s)
- Aileen Ritter
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60486 Frankfurt am Main, Germany; (J.H.); (S.B.); (D.H.); (I.M.); (L.L.); (B.W.)
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Guo S, Liu Q, Tan T, Chen X. MiR-24 regulates obstructive pulmonary disease in rats via S100A8. Exp Lung Res 2024; 50:172-183. [PMID: 39390946 DOI: 10.1080/01902148.2024.2411852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 09/05/2024] [Accepted: 09/28/2024] [Indexed: 10/12/2024]
Abstract
PURPOSE Chronic obstructive pulmonary disease (COPD) is a persistent inflammatory disorder characterized by minor airway inflammation and emphysema involving various cell types and cytokines. MicroRNAs (miRNAs) have emerged as critical regulators in the pathogenesis of lung diseases. This study investigates the impact of microRNA-24 (miR-24) on airway inflammatory responses in a rat model of COPD. MATERIALS AND METHODS The model was established by combining cigarette smoke exposure and lipopolysaccharide stimulation, and rat lung tissues were transfected with adeno-associated viruses overexpressing miR-24. Pathological changes in the lung were assessed using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, and interleukin-8, were measured using enzyme-linked immunosorbent assay. Expression of miR-24 and S100A8 was detected through quantitative reverse transcription PCR, while protein levels of S100A8, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were assessed using western blotting. Bioinformatics analysis and dual-luciferase reporter assay were performed to determine the relationship between S100A8 and miR-24. RESULTS The results demonstrated the downregulation of miR-24 in rats with COPD, and its overexpression resulted in a significant decrease in S1008 mRNA levels. Additionally, the protein level of S100A8 was significantly increased in the lung tissues of COPD rats. The upregulation of miR-24, however, not only inhibited the protein expression of S100A8, TLR4, and MyD88 in lung tissues but also reduced the release of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid, thereby attenuating inflammatory responses and pathological injuries in the lung. CONCLUSIONS Our data suggest that miR-24 attenuates airway inflammatory responses in COPD by inhibiting the TLR4/MyD88 pathway via targeting S100A8.
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Affiliation(s)
- Sha Guo
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Qin Liu
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Tingting Tan
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xiaoju Chen
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
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48
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Xing N, Gao L, Xie W, Deng H, Yang F, Liu D, Li A, Pang Q. Mining of potentially stem cell-related miRNAs in planarians. Mol Biol Rep 2024; 51:1045. [PMID: 39377855 DOI: 10.1007/s11033-024-09977-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 09/27/2024] [Indexed: 10/09/2024]
Abstract
Stem cells and regenerative medicine have recently become important research topics. However, the complex stem cell regulatory networks involved in various microRNA (miRNA)-mediated mechanisms have not yet been fully elucidated. Planarians are ideal animal models for studying stem cells owing to their rich stem cell populations (neoblasts) and extremely strong regeneration capacity. The roles of planarian miRNAs in stem cells and regeneration have long attracted attention. However, previous studies have generally provided simple datasets lacking integrative analysis. Here, we have summarized the miRNA family reported in planarians and highlighted conservation in both sequence and function. Furthermore, we summarized miRNA data related to planarian stem cells and regeneration and screened potential involved candidates. Nevertheless, the roles of these miRNAs in planarian regeneration and stem cells remain unclear. The identification of potential stem cell-related miRNAs offers more precise suggestions and references for future investigations of miRNAs in planarians. Furthermore, it provides potential research avenues for understanding the mechanisms of stem cell regulatory networks. Finally, we compiled a summary of the experimental methods employed for studying planarian miRNAs, with the aim of highlighting special considerations in certain procedures and providing more convenient technical support for future research endeavors.
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Affiliation(s)
- Nianhong Xing
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China
| | - Lili Gao
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China.
| | - Wenshuo Xie
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China
| | - Hongkuan Deng
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China
| | - Fengtang Yang
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China
| | - Dongwu Liu
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China
| | - Ao Li
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China
| | - Qiuxiang Pang
- Anti-aging & Regenerative Medicine Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China.
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49
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Hongfang G, Khan R, El-Mansi AA. Bioinformatics Analysis of miR-181a and Its Role in Adipogenesis, Obesity, and Lipid Metabolism Through Review of Literature. Mol Biotechnol 2024; 66:2710-2724. [PMID: 37773313 DOI: 10.1007/s12033-023-00894-w] [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: 05/03/2023] [Accepted: 09/04/2023] [Indexed: 10/01/2023]
Abstract
The miRNAs regulate various biological processes in the mammalian body system. The role of miR-181a in the development, progression, and expansion of cancers is well-documented. However, the role of miR-181a in adipogenesis; lipid metabolism; obesity; and obesity-related issues such as diabetes mellitus needs to be explored. Therefore, in the present study, the literature was searched and bioinformatics tools were applied to explore the role of miR-181a in adipogenesis. The list of adipogenic and lipogenic target genes validated through different publications were extracted and compiled. The network and functional analysis of these target genes was performed through in-silico analysis. The mature sequence of miR-181a of different species were extracted from and were found highly conserved among the curated species. Additionally, we also used various bioinformatics tools such as target gene extraction from Targetscan, miRWalk, and miRDB, and the list of the target genes from these different databases was compared, and common target genes were predicted. These common target genes were further subjected to the enrichment score and KEGG pathways analysis. The enrichment score of the vital KEGG pathways of the target genes is the key regulator of adipogenesis, lipogenesis, obesity, and obesity-related syndromes in adipose tissues. Therefore, the information presented in the current review will explore the regulatory roles of miR-181a in fat tissues and its associated functions and manifestations.
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Affiliation(s)
- Guo Hongfang
- Medical College of Xuchang University, No.1389, Xufan Road, Xuchang City, 461000, Henan Province, People's Republic of China
| | - Rajwali Khan
- Department of Livestock Management, Breeding and Genetics, The University of Agriculture, Peshawar, 25130, Pakistan.
| | - Ahmed A El-Mansi
- Biology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia
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50
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Moses AS, Korzun T, Mamnoon B, Baldwin MK, Myatt L, Taratula O, Taratula OR. Nanomedicines for Improved Management of Ectopic Pregnancy: A Narrative Review. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2301873. [PMID: 37471169 PMCID: PMC10837845 DOI: 10.1002/smll.202301873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/04/2023] [Indexed: 07/22/2023]
Abstract
Ectopic pregnancy (EP) - the implantation of an embryo outside of the endometrial cavity, often in the fallopian tube - is a significant contributor to maternal morbidity and leading cause of maternal death due to hemorrhage in first trimester. Current diagnostic modalities including human chorionic gonadotropin (hCG) quantification and ultrasonography are effective, but may still misdiagnose EP at initial examination in many cases. Depending on the patient's hemodynamic stability and gestational duration of the pregnancy, as assessed by history, hCG measurement and ultrasonography, management strategies may include expectant management, chemotherapeutic treatment using methotrexate (MTX), or surgical intervention. While these strategies are largely successful, expectant management may result in tubal rupture if the pregnancy does not resolve spontaneously; MTX administration is not always successful and may induce significant side effects; and surgical intervention may result in loss of the already-damaged fallopian tube, further hampering the patient's subsequent attempts to conceive. Nanomaterial-based technologies offer the potential to enhance delivery of diagnostic imaging contrast and therapeutic agents to more effectively and safely manage EP. The purpose of this narrative review is to summarize the current state of nanomedicine technology dedicated to its potential to improve both the diagnosis and treatment of EP.
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Affiliation(s)
- Abraham S Moses
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Tetiana Korzun
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Babak Mamnoon
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Maureen K Baldwin
- Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA
| | - Leslie Myatt
- Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA
| | - Oleh Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Olena R Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
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