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Li L, Wei C, Xie Y, Su Y, Liu C, Qiu G, Liu W, Liang Y, Zhao X, Huang D, Wu D. Expanded insights into the mechanisms of RNA-binding protein regulation of circRNA generation and function in cancer biology and therapy. Genes Dis 2025; 12:101383. [PMID: 40290118 PMCID: PMC12022641 DOI: 10.1016/j.gendis.2024.101383] [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: 02/26/2024] [Revised: 05/06/2024] [Accepted: 06/22/2024] [Indexed: 04/30/2025] Open
Abstract
RNA-binding proteins (RBPs) regulate the generation of circular RNAs (circRNAs) by participating in the reverse splicing of circRNA and thereby influencing circRNA function in cells and diseases, including cancer. Increasing evidence has demonstrated that the circRNA-RBP network plays a complex and multifaceted role in tumor progression. Thus, a better understanding of this network may provide new insights for the discovery of cancer drugs. In this review, we discuss the characteristics of RBPs and circRNAs and how the circRNA-RBP network regulates tumor cell phenotypes such as proliferation, metastasis, apoptosis, metabolism, immunity, drug resistance, and the tumor environment. Moreover, we investigate the factors that influence circRNA-RBP interactions and the regulation of downstream pathways related to tumor development, such as the tumor microenvironment and N6-methyladenosine modification. Furthermore, we discuss new ideas for targeting circRNA-RBP interactions using various RNA technologies.
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Affiliation(s)
- Lixia Li
- Cancer Hospital, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Chunhui Wei
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Yu Xie
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Yanyu Su
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Caixia Liu
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Guiqiang Qiu
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Weiliang Liu
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Yanmei Liang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Xuanna Zhao
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Dan Huang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
| | - Dong Wu
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, China
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Lu Z, Ni W, Wu Y, Zhai B, Zhao Q, Zheng T, Liu Q, Ding D. Application of biomarkers in the diagnosis of kidney disease. Front Med (Lausanne) 2025; 12:1560222. [PMID: 40370722 PMCID: PMC12075424 DOI: 10.3389/fmed.2025.1560222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/16/2025] [Indexed: 05/16/2025] Open
Abstract
Worldwide, kidney disease has grown to be an important global public health agenda that reduces longevity. Medical institutions around the globe should enhance screening efforts for kidney disease, to facilitate early kidney disease detection, diagnosis, and intervention. Common screening methods for nephropathy encompass renal tissue biopsy, urine dry chemistry tests, urine formed element analysis, and urine-specific protein assays, among others. These methodologies evaluate renal health by scrutinizing a spectrum of biomarkers. Precise classification and quantitative analysis of these biomarkers can assist in determining the site and extent of kidney injury, as well as in assessing treatment efficacy and prognosis. In this paper, we reviewed the methods and biomarkers for kidney disease and also the integration of multiple biomarkers. With the aim of reasonable applying these markers to the early detection, accurate diagnosis, and scientific management of kidney disease, thereby mitigating the threat posed by kidney disease to human health.
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Affiliation(s)
- Zuohua Lu
- Department of Clinical Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
| | - Weifeng Ni
- Department of Endocrinology, Rheumatology and Immunology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yuding Wu
- Goldsite Diagnostics Inc., Shenzhen, China
| | - Bin Zhai
- Department of Clinical Laboratory, Baotou Central Hospital, Baotou, China
| | - Qiuyun Zhao
- Department of Clinical Laboratory, Guilin Hospital of Integrated Traditional Chinese and Western Medicine, Guilin, China
| | - Tian Zheng
- Department of Clinical Laboratory, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Qianqian Liu
- Department of Clinical Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
| | - Dapeng Ding
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
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3
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Li S, Hu W, Qian L, Sun D. Insights into non-coding RNAS: biogenesis, function and their potential regulatory roles in acute kidney disease and chronic kidney disease. Mol Cell Biochem 2025; 480:1287-1304. [PMID: 39110280 PMCID: PMC11842482 DOI: 10.1007/s11010-024-05083-0] [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: 05/05/2024] [Accepted: 07/29/2024] [Indexed: 01/03/2025]
Abstract
Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.
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Affiliation(s)
- Shulin Li
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Wanru Hu
- Central Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Luoxiang Qian
- Central Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Dong Sun
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
- Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China.
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4
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Zeng J, Luo C, Jiang Y, Hu T, Lin B, Xie Y, Lan J, Miao J. Decoding TDP-43: the molecular chameleon of neurodegenerative diseases. Acta Neuropathol Commun 2024; 12:205. [PMID: 39736783 DOI: 10.1186/s40478-024-01914-9] [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: 09/22/2024] [Accepted: 12/13/2024] [Indexed: 01/01/2025] Open
Abstract
TAR DNA-binding protein 43 (TDP-43) has emerged as a critical player in neurodegenerative disorders, with its dysfunction implicated in a wide spectrum of diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer's disease (AD). This comprehensive review explores the multifaceted roles of TDP-43 in both physiological and pathological contexts. We delve into TDP-43's crucial functions in RNA metabolism, including splicing regulation, mRNA stability, and miRNA biogenesis. Particular emphasis is placed on recent discoveries regarding TDP-43's involvement in DNA interactions and chromatin dynamics, highlighting its broader impact on gene expression and genome stability. The review also examines the complex pathogenesis of TDP-43-related disorders, discussing the protein's propensity for aggregation, its effects on mitochondrial function, and its non-cell autonomous impacts on glial cells. We provide an in-depth analysis of TDP-43 pathology across various neurodegenerative conditions, from well-established associations in ALS and FTLD to emerging roles in diseases such as Huntington's disease and Niemann-Pick C disease. The potential of TDP-43 as a therapeutic target is explored, with a focus on recent developments in targeting cryptic exon inclusion and other TDP-43-mediated processes. This review synthesizes current knowledge on TDP-43 biology and pathology, offering insights into the protein's central role in neurodegeneration and highlighting promising avenues for future research and therapeutic interventions.
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Affiliation(s)
- Jixiang Zeng
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China
| | - Chunmei Luo
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China
| | - Yang Jiang
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China
| | - Tao Hu
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China
| | - Bixia Lin
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China
| | - Yuanfang Xie
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China
| | - Jiao Lan
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China.
| | - Jifei Miao
- Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guang Dong, 518000, China.
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Hejazian SM, Rahbar Saadat Y, Hosseiniyan Khatibi SM, Farnood F, Farzamikia N, Hejazian SS, Batoumchi S, Shoja MM, Zununi Vahed S, Ardalan M. Circular RNAs as novel biomarkers in glomerular diseases. Arch Physiol Biochem 2024; 130:568-580. [PMID: 37194131 DOI: 10.1080/13813455.2023.2212328] [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: 10/19/2022] [Revised: 05/03/2023] [Accepted: 05/03/2023] [Indexed: 05/18/2023]
Abstract
Circular RNAs (circRNAs) regulate gene expression and biological procedures by controlling target genes or downstream pathways by sponging their related miRNA (s). Three types of circRNAs have been identified; exonic circRNAs (ecircRNAs), intronic RNAs (ciRNAs), and exon-intron circRNAs (ElciRNAs). It is clarified that altered levels of circRNAs have dynamic pathological and physiological functions in kidney diseases. Evidence suggests that circRNAs can be considered novel diagnostic biomarkers and therapeutic targets for renal diseases. Glomerulonephritis (GN) is a general term used to refer to a wide range of glomerular diseases. GN is an important cause of chronic kidney diseases. Here, we review the biogenesis of circRNAs, and their molecular and physiological functions in the kidney. Moreover, the dysregulated expression of circRNAs and their biological functions are discussed in primary and secondary glomerulonephritis. Moreover, diagnostic and therapeutic values of circRNAs in distinguishing or treating different types of GN are highlighted.
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Affiliation(s)
| | | | | | - Farahnoosh Farnood
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Negin Farzamikia
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyyed Sina Hejazian
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sepideh Batoumchi
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammadali M Shoja
- College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
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Holme FA, Huse C, Kong XY, Broch K, Gullestad L, Anstensrud AK, Andersen GØ, Amundsen BH, Kleveland O, Quiles-Jimenez A, Holm S, Aukrust P, Alseth I, Halvorsen B, Dahl TB. Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction. Int J Mol Sci 2024; 25:9014. [PMID: 39201700 PMCID: PMC11354517 DOI: 10.3390/ijms25169014] [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: 06/20/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/03/2024] Open
Abstract
Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and ApoE-/- mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab (n = 21) or placebo (n = 19) was collected at admission, 3-7 days, and at 6 months, in addition to samples from healthy controls (n = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3-7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function.
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Affiliation(s)
- Fredric A. Holme
- Institute of Clinical Medicine, University of Oslo (UiO), 0372 Oslo, Norway (B.H.)
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Camilla Huse
- Institute of Clinical Medicine, University of Oslo (UiO), 0372 Oslo, Norway (B.H.)
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
- Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Xiang Yi Kong
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Kaspar Broch
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway (A.K.A.)
| | - Lars Gullestad
- Institute of Clinical Medicine, University of Oslo (UiO), 0372 Oslo, Norway (B.H.)
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway (A.K.A.)
| | | | - Geir Ø. Andersen
- Department of Cardiology, Oslo University Hospital, Ullevål, 0450 Oslo, Norway;
| | - Brage H. Amundsen
- Clinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway
| | - Ola Kleveland
- Clinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Ana Quiles-Jimenez
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Sverre Holm
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Pål Aukrust
- Institute of Clinical Medicine, University of Oslo (UiO), 0372 Oslo, Norway (B.H.)
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Ingrun Alseth
- Department of Microbiology, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Bente Halvorsen
- Institute of Clinical Medicine, University of Oslo (UiO), 0372 Oslo, Norway (B.H.)
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
| | - Tuva B. Dahl
- Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway
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Filomena A, Giovanni S, Ginevra S, Santiago N, Di Fasano Miriam S, Peppino M, Alessandra C, Antonia DM, Giuliana B, Rosanna P, Marco S, Lorena B. Identification of a circular RNA isoform of WASHC2A as a prognostic factor for high-risk paediatric B-ALL patients. Biomed Pharmacother 2024; 177:116903. [PMID: 38917755 DOI: 10.1016/j.biopha.2024.116903] [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: 03/26/2024] [Revised: 05/24/2024] [Accepted: 06/06/2024] [Indexed: 06/27/2024] Open
Abstract
Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed. Circular RNAs (circRNAs) are promising markers due to their stability and differential expression patterns in various diseases. However, their role in pediatric B-ALL patients, particularly in risk stratification and relapse prediction, remains poorly understood. In this study, we comprehensively examined the circRNA landscape in pediatric B-ALL patients, focusing on both high-risk and standard-risk patients. Using advanced sequencing techniques and sophisticated bioinformatics tools, we identified thousands of circRNAs, including a novel circRNA derived from the WASHC2A gene, termed circWASHC2A. CircWASHC2A showed differential expression between high-risk and standard-risk patients and exhibited potential for predicting relapse in high-risk patients. Functional experiments highlighted a role for circWASHC2A in regulating cell cycle progression and mitochondrial respiratory activity in leukaemic cells. Transcriptomic analysis further supported these findings, suggesting the involvement of circWASHC2A in signalling pathways relevant to leukaemia pathogenesis. This study provides in-depth insights into the circRNA landscape of pediatric B-ALL patients and identifies circWASHC2A as a potential biomarker for risk stratification and relapse prediction, with significant implications for tailoring diagnostic and therapeutic strategies in this patient population.
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Affiliation(s)
| | | | | | | | | | - Mirabelli Peppino
- Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, AORN, Naples 80122, Italy
| | - Cianflone Alessandra
- Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, AORN, Naples 80122, Italy
| | - De Matteo Antonia
- Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, AORN, Naples 80122, Italy
| | - Beneduce Giuliana
- Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, AORN, Naples 80122, Italy
| | - Parasole Rosanna
- Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, AORN, Naples 80122, Italy
| | | | - Buono Lorena
- IRCCS SYNLAB SDN, Via E. Gianturco 113, Naples 80143, Italy.
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Tuerdi R, Zhang H, Wang W, Shen M, Wei X. Bibliometric analysis of the research hotspots and trends of circular RNAs. Heliyon 2024; 10:e31478. [PMID: 38818139 PMCID: PMC11137546 DOI: 10.1016/j.heliyon.2024.e31478] [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: 11/29/2023] [Revised: 03/27/2024] [Accepted: 05/16/2024] [Indexed: 06/01/2024] Open
Abstract
Background and objective Circular RNAs (circRNAs) have garnered considerable attention in the study of various human diseases due to their ubiquitous expression and potential biological functions. This study conducts a bibliometric and visualization-based analysis of circRNA-related research in diseases, aiming to reveal the current status, hotspots and emerging trends within the field. Methods Literature published between 2013 and 2022 and indexed in the Web of Science core databases was retrieved. Visualizations of publication volume, countries, authors, institutions, journals, references, and keywords were performed. Microsoft Excel (2021) was used to analyze and graph publication volume and growth trends. Additionally, CiteSpace (version 6.1.R6) and VOSviewer (version 1.6.18) were employed to visualize the bibliographic information. Results Between 2013 and 2022, a total of 4195 relevant articles on circRNA in the context of diseases were identified. These articles covered 56 countries, 2528 institutions, 19,842 authors and 698 journals, citing 85,541 references. The annual publication volume showed an exponential growth trend, with rapid development post-2017. China, the United States and Germany emerged as the top three contributors, demonstrating high publication volume and total citations. Notably, Nanjing Medical University exhibited the highest publication volume, boasting 291 articles. Burton B. Yang and Li Yang consistently ranked among the top 10 authors in terms of publication volume and citations, emerging as core contributors in this research field. The journal Bioengineered ranked first in terms of published articles (160), with an impact factor of 6.832, while Molecular Cancer garnered the highest impact factor (41.4), solidifying its position as a top journal in this field. Furthermore, high-frequency keywords included "expression" "proliferation" "biomarker" "microRNA" "cancer", signifying the prevailing research hotspots and principal themes of this field over the past decade. As of 2022, "biomarker", "prostate cancer","drug resistance","papillary thyroid carcinoma", etc. continued as keywords during the outbreak period. At present, the value of circRNA application is mainly reflected in the two aspects of biomarkers and therapeutic targets, and the prediction of accurate diagnosis and precise treatment based on big data analysis, especially in cancer, will become a hot spot of research in the future. Conclusion The trajectory of circRNA research from its biological origins to its applications in diseases has been delineated from 2013 to 2022. However, the transition to disease-specific applications and exploration of biological functions warrants further attention in future research endeavors.
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Affiliation(s)
- Reyila Tuerdi
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Hui Zhang
- Pathogenic Biology Laboratory, Gansu Provincial Center for Disease Prevention and Control, Lanzhou, 730000, Gansu, China
| | - Wenxin Wang
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Minghui Shen
- Center of Laboratory Medicine, Lanzhou University Second Hospital, Lanzhou, 730000, Gansu, China
| | - Xingmin Wei
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
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9
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Cheng F, Chapman T, Zhang S, Morsch M, Chung R, Lee A, Rayner SL. Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease. Ageing Res Rev 2024; 96:102246. [PMID: 38401571 DOI: 10.1016/j.arr.2024.102246] [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: 10/26/2023] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 02/26/2024]
Abstract
TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circular RNA. These changes can result in the generation of an altered transcriptome and proteome within cells, ultimately changing the diversity and quantity of gene products. In this review, we summarise the findings of novel atypical RNAs resulting from TDP-43 dysfunction and their potential as biomarkers or targets for therapeutic development.
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Affiliation(s)
- Flora Cheng
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia.
| | - Tyler Chapman
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia
| | - Selina Zhang
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia
| | - Marco Morsch
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia
| | - Roger Chung
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia
| | - Albert Lee
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia
| | - Stephanie L Rayner
- Motor Neuron Disease Research Centre, Macquarie Medical School, Macquarie University, Sydney, Australia.
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10
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Gutierrez-Camino A, Caron M, Richer C, Fuchs C, Illarregi U, Poncelet L, St-Onge P, Bataille AR, Tremblay-Dauphinais P, Lopez-Lopez E, Camos M, Ramirez-Orellana M, Astigarraga I, Lécuyer É, Bourque G, Martin-Guerrero I, Sinnett D. CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in TCF3::PBX1 ALL. Int J Mol Sci 2024; 25:1477. [PMID: 38338754 PMCID: PMC10855129 DOI: 10.3390/ijms25031477] [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: 11/10/2023] [Revised: 01/15/2024] [Accepted: 01/18/2024] [Indexed: 02/12/2024] Open
Abstract
Childhood B-cell acute lymphoblastic leukemia (B-ALL) is a heterogeneous disease comprising multiple molecular subgroups with subtype-specific expression profiles. Recently, a new type of ncRNA, termed circular RNA (circRNA), has emerged as a promising biomarker in cancer, but little is known about their role in childhood B-ALL. Here, through RNA-seq analysis in 105 childhood B-ALL patients comprising six genetic subtypes and seven B-cell controls from two independent cohorts we demonstrated that circRNAs properly stratified B-ALL subtypes. By differential expression analysis of each subtype vs. controls, 156 overexpressed and 134 underexpressed circRNAs were identified consistently in at least one subtype, most of them with subtype-specific expression. TCF3::PBX1 subtype was the one with the highest number of unique and overexpressed circRNAs, and the circRNA signature could effectively discriminate new patients with TCF3::PBX1 subtype from others. Our results indicated that NUDT21, an RNA-binding protein (RBP) involved in circRNA biogenesis, may contribute to this circRNA enrichment in TCF3::PBX1 ALL. Further functional characterization using the CRISPR-Cas13d system demonstrated that circBARD1, overexpressed in TCF3::PBX1 patients and regulated by NUDT21, might be involved in leukemogenesis through the activation of p38 via hsa-miR-153-5p. Our results suggest that circRNAs could play a role in the pathogenesis of childhood B-ALL.
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Affiliation(s)
- Angela Gutierrez-Camino
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Maxime Caron
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
- Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada;
| | - Chantal Richer
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Claire Fuchs
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Unai Illarregi
- Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; (U.I.); (I.M.-G.)
| | - Lucas Poncelet
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Pascal St-Onge
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Alain R. Bataille
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Pascal Tremblay-Dauphinais
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
| | - Elixabet Lopez-Lopez
- Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
- Pediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain;
| | - Mireia Camos
- Hematology Laboratory, Sant Joan de Déu Research Institute, Esplugues de Llobregat, 08950 Barcelona, Spain;
| | - Manuel Ramirez-Orellana
- Department of Pediatric Hematology and Oncology, Niño Jesús University Hospital, 28009 Madrid, Spain;
| | - Itziar Astigarraga
- Pediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain;
- Department of Pediatrics, Cruces University Hospital, 48903 Barakaldo, Spain
| | - Éric Lécuyer
- Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada;
- Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montreal, QC H3C 3J7, Canada
- Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada
| | - Guillaume Bourque
- Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada;
| | - Idoia Martin-Guerrero
- Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; (U.I.); (I.M.-G.)
- Pediatric Oncology Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain;
| | - Daniel Sinnett
- Division of Hematology-Oncology, CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; (A.G.-C.); (M.C.); (C.R.); (C.F.); (L.P.); (P.S.-O.); (A.R.B.); (P.T.-D.)
- Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada
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11
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Zhang ZH, Wang Y, Zhang Y, Zheng SF, Feng T, Tian X, Abudurexiti M, Wang ZD, Zhu WK, Su JQ, Zhang HL, Shi GH, Wang ZL, Cao DL, Ye DW. The function and mechanisms of action of circular RNAs in Urologic Cancer. Mol Cancer 2023; 22:61. [PMID: 36966306 PMCID: PMC10039696 DOI: 10.1186/s12943-023-01766-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 03/17/2023] [Indexed: 03/27/2023] Open
Abstract
Kidney, bladder, and prostate cancer are the three major tumor types of the urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding RNAs with a stabile structure and a unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs are widely distributed within the body, with important biologic functions such as sponges for microRNAs, as RNA binding proteins, and as templates for regulation of transcription and protein translation. The abnormal expression of circRNAs in vivo is significantly associated with the development of urologic tumors. CircRNAs have now emerged as potential biomarkers for the diagnosis and prognosis of urologic tumors, as well as targets for the development of new therapies. Although we have gained a better understanding of circRNA, there are still many questions to be answered. In this review, we summarize the properties of circRNAs and detail their function, focusing on the effects of circRNA on proliferation, metastasis, apoptosis, metabolism, and drug resistance in kidney, bladder, and prostate cancers.
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Affiliation(s)
- Zi-Hao Zhang
- Qingdao Institute, School of Life Medicine, Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Qingdao, 266500, China
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Yue Wang
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Ya Zhang
- Department of Nephrology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China
| | - Sheng-Feng Zheng
- Qingdao Institute, School of Life Medicine, Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Qingdao, 266500, China
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Tao Feng
- Qingdao Institute, School of Life Medicine, Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Qingdao, 266500, China
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Xi Tian
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Mierxiati Abudurexiti
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
- Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China
| | - Zhen-Da Wang
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Wen-Kai Zhu
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Jia-Qi Su
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Hai-Liang Zhang
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Guo-Hai Shi
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Zi-Liang Wang
- Institute of Cancer Research, Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, P. R. China
| | - Da-Long Cao
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China
| | - Ding-Wei Ye
- Department of Urology, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200433, China.
- Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China.
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12
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Structural Modifications of siRNA Improve Its Performance In Vivo. Int J Mol Sci 2023; 24:ijms24020956. [PMID: 36674473 PMCID: PMC9862127 DOI: 10.3390/ijms24020956] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/23/2022] [Accepted: 12/26/2022] [Indexed: 01/06/2023] Open
Abstract
The use of small interfering RNA (siRNA) in the clinic gives a wide range of possibilities for the treatment of previously incurable diseases. However, the main limitation for biomedical applications is their delivery to target cells and organs. Currently, delivery of siRNA to liver cells is a solved problem due to the bioconjugation of siRNA with N-acetylgalactosamine; other organs remain challenging for siRNA delivery to them. Despite the important role of the ligand in the composition of the bioconjugate, the structure and molecular weight of siRNA also play an important role in the delivery of siRNA. The basic principle is that siRNAs with smaller molecular weights are more efficient at entering cells, whereas siRNAs with larger molecular weights have advantages at the organism level. Here we review the relationships between siRNA structure and its biodistribution and activity to find new strategies for improving siRNA performance.
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13
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Study on the Mechanism of circRNA Regulating the miRNA Level in Nephrotic Syndrome. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3729995. [PMID: 35859997 PMCID: PMC9293565 DOI: 10.1155/2022/3729995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 06/10/2022] [Accepted: 06/17/2022] [Indexed: 12/02/2022]
Abstract
Background Nephrotic syndrome is an enormous public healthy threaten, which causes a variety of complications and secondary disease; however, the molecular mechanism of nephrotic syndrome remains unclear. Methods In our study, RNA-seq were used to test the transcription level of patients with nephrotic syndrome, in order to investigate the interaction of circRNA-miRNA-mRNA in nephrotic syndrome patients. Results Consistent with our hypothesis, miRNAs were confirmed to be associated with nephrotic syndrome, majority of their targeting circRNAs downregulated in nephrotic syndrome patients and at the same time, the KEGG pathway analysis found that target genes of the circRNAs bonding miRNAs was highly correlated with the occurrence of kidney diseases. Conclusion Thus, we can draw a conclusion that downregulated circRNAs cause miRNA expressing aberrant and then affect the expression level of mRNA, finally leading to the generation of nephrotic syndrome.
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Li B, Lin F, Xia Y, Ye Z, Yan X, Song B, Yuan T, Li L, Zhou X, Yu W, Cheng F. The Intersection of Acute Kidney Injury and Non-Coding RNAs: Inflammation. Front Physiol 2022; 13:923239. [PMID: 35755446 PMCID: PMC9218900 DOI: 10.3389/fphys.2022.923239] [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: 04/19/2022] [Accepted: 05/16/2022] [Indexed: 12/02/2022] Open
Abstract
Acute renal injury (AKI) is a complex clinical syndrome, involving a series of pathophysiological processes, in which inflammation plays a key role. Identification and verification of gene signatures associated with inflammatory onset and progression are imperative for understanding the molecular mechanisms involved in AKI pathogenesis. Non-coding RNAs (ncRNAs), involved in epigenetic modifications of inflammatory responses, are associated with the aberrant expression of inflammation-related genes in AKI. However, its regulatory role in gene expression involves precise transcriptional regulation mechanisms which have not been fully elucidated in the complex and volatile inflammatory response of AKI. In this study, we systematically review current research on the intrinsic molecular mechanisms of ncRNAs that regulate the inflammatory response in AKI. We aim to provide potential research directions and strategies for developing ncRNA-targeted gene therapies as an intervention for the inflammatory damage in AKI.
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Affiliation(s)
- Bojun Li
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Fangyou Lin
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuqi Xia
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zehua Ye
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xinzhou Yan
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Baofeng Song
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Tianhui Yuan
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Lei Li
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiangjun Zhou
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Weimin Yu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Fan Cheng
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
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15
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Wei L, Yu Z, Liu L, Zhou Y, Bai X, Wang L, Bai M, Sun S. Integrated Analysis of the CircRNA-Based ceRNA Network in Renal Fibrosis Induced by Ischemia Reperfusion Injury. Front Genet 2022; 12:793182. [PMID: 35222519 PMCID: PMC8866765 DOI: 10.3389/fgene.2021.793182] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/29/2021] [Indexed: 12/16/2022] Open
Abstract
Background: Circular RNAs (circRNAs), which have broad posttranscriptional regulatory potencies, are involved in the pathogenesis of fibrotic diseases and are promising diagnostic biomarkers and therapeutic targets. However, their specific roles in renal fibrosis remain elusive. Methods: A robust unilateral renal ischemia reperfusion injury (UIRI) mouse model was established to recapitulate the pathophysiology of renal fibrosis. The expression of circRNAs, miRNAs, and mRNAs was profiled by high-throughput RNA sequencing technology. Results: In total, 4983 circRNAs, 216 miRNAs, and 6371 mRNAs were differentially expressed in UIRI-induced fibrotic kidneys. Candidate circRNAs and miRNAs were validated by RT–qPCR in both UIRI and unilateral ureteral obstruction mouse models. Bioinformatic analysis indicated that the parental genes of the differentially expressed circRNAs were predominantly implicated in focal adhesion, adhesion junctions, and regulation of actin cytoskeleton pathways. Through circRNA-miRNA-mRNA construction, we identified two hub genes, circSlc8a1 and circApoe, that targeted a large number of differentially expressed miRNAs and mRNAs related to metabolism and cytokine–cytokine receptor pathways, respectively. Conclusion: CircRNAs were dysregulated in the UIRI model and might be potentially involved in the pathogenesis of renal fibrosis. Research efforts should focus on unravelling the functions of aberrantly expressed circRNAs in renal fibrosis to uncover biomarkers that would enable early diagnosis and the design of prompt therapeutic interventions to prevent disease progression.
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Affiliation(s)
- Lei Wei
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
| | - Zhixiang Yu
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
| | - Limin Liu
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Ying Zhou
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
| | - Xiao Bai
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
| | - Liya Wang
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
| | - Ming Bai
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Shiren Sun
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- *Correspondence: Shiren Sun,
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