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1
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Habara A. Exploratory Review and In Silico Insights into circRNA and RNA-Binding Protein Roles in γ-Globin to β-Globin Switching. Cells 2025; 14:312. [PMID: 39996784 PMCID: PMC11854342 DOI: 10.3390/cells14040312] [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: 01/11/2025] [Revised: 02/16/2025] [Accepted: 02/18/2025] [Indexed: 02/26/2025] Open
Abstract
β-globin gene cluster regulation involves complex mechanisms to ensure proper expression and function in RBCs. During development, switching occurs as γ-globin is replaced by β-globin. Key regulators, like BCL11A and ZBTB7A, repress γ-globin expression to facilitate this transition with other factors, like KLF1, LSD1, and PGC-1α; these regulators ensure an orchestrated transition from γ- to β-globin during development. While these mechanisms have been extensively studied, circRNAs have recently emerged as key contributors to gene regulation, but their role in β-globin gene cluster regulation remains largely unexplored. Although discovered in the 1970s, circRNAs have only recently been recognized for their functional roles, particularly in interactions with RNA-binding proteins. Understanding how circRNAs contribute to switching from γ- to β-globin could lead to new therapeutic strategies for hemoglobinopathies, such as sickle cell disease and β-thalassemia. This review uses the circAtlas 3.0 database to explore circRNA expressions in genes related to switching from γ- to β-globin expression, focusing on blood, bone marrow, liver, and spleen. It emphasizes the exploration of the potential interactions between circRNAs and RNA-binding proteins involved in β-globin gene cluster regulatory mechanisms, further enhancing our understanding of β-globin gene cluster expression.
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Affiliation(s)
- Alawi Habara
- Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
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2
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Chen Y, Bao L, Dong F, Xv M, Li W, Luo T, Xing C, Yan N, Niu K, Zhang N, Fan H. Effect of fibroblasts small- conductance Ca 2+ -activated potassium channel subtype 2 (SK2) on myocardial fibrosis in pressure overload mouse. Cell Signal 2024; 124:111401. [PMID: 39260533 DOI: 10.1016/j.cellsig.2024.111401] [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: 06/26/2024] [Revised: 08/30/2024] [Accepted: 09/06/2024] [Indexed: 09/13/2024]
Abstract
Studies have shown that Small conductance Ca2 + -activated K+ (SK) channel are expressed in fibroblasts. We aimed to determine the expression of SK2 channels in cardiac fibroblasts during myocardial hypertrophy and investigate its relationship with fibrotic remodeling. Myocardial hypertrophy and fibrotic remodeling induced by transverse aortic constriction (TAC) were assessed by echocardiography, Masson's trichrome staining and Western blot. Knockdown and overexpression of the SK2 protein were used to assess relationship between SK2 expression in fibroblasts and myocardial fibrosis. There is a positive correlation between myocardial fibrosis and SK2 channel protein expression during the development of myocardial hypertrophy. The differentiation and secretion of fibroblasts in mice with cardiac hypertrophy are enhanced, and the expression of SK2 channel protein is increased. Manipulating SK2 levels in fibroblasts can either promote or inhibit their differentiation and secretory function. Knocking down SK2 reduces the up-regulation of TGF β1, p-Smad2/3/GAPDH, p-p38/GAPDH, p-ERK1/2/GAPDH, and p-JNK/GAPDH proteins induced by Ang II in cardiac fibroblasts without significantly affecting total protein levels. AAV9-SK2-RNAi injection in mice improves cardiac function. Collectively, our study suggests that the expression of the SK2 channel is significantly increased in fibroblasts of mice with myocardial hypertrophy, potentially impacting myocardial fibrosis remodeling via the TGF-β signaling pathway.
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Affiliation(s)
- Yihan Chen
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Limeng Bao
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Fengjuan Dong
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Menru Xv
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Weidong Li
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Tianxia Luo
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Chenxv Xing
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Ningning Yan
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Kangli Niu
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Ningyuan Zhang
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China
| | - Hongkun Fan
- Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, No.100 Kexuedadao Road, Zhengzhou 450000, China.
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Sharma A, Bansal C, Sharma KL, Kumar A. Circular RNA: The evolving potential in the disease world. World J Med Genet 2024; 12:93011. [DOI: 10.5496/wjmg.v12.i1.93011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/23/2024] [Accepted: 07/02/2024] [Indexed: 09/19/2024] Open
Abstract
Circular RNAs (circRNAs), a new star of noncoding RNAs, are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome. Most circRNAs are conserved throughout species and frequently show stage-specific expression during various stages of tissue development. CircRNAs were a mystery discovery, as they were initially believed to be a product of splicing errors; however, subsequent research has shown that circRNAs can perform various functions and help in the regulation of splicing and transcription, including playing a role as microRNA (miRNA) sponges. With the application of high throughput next-generation technologies, circRNA hotspots were discovered. There are emerging indications that explain the association of circRNAs with human diseases, like cancers, developmental disorders, and inflammation, and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases, including cancer. After the discoveries of miRNAs and long noncoding RNAs, circRNAs are now acting as a novel research entity of interest in the field of RNA disease biology. In this review, we aim to focus on major updates on the biogeny and metabolism of circRNAs, along with their possible/established roles in major human diseases.
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Affiliation(s)
- Aarti Sharma
- Department of Research, Mayo Clinic Arizona, Phoenix, AZ 85054, United States
| | - Cherry Bansal
- Department of Pathology, Dr. S Tantia Medical College, Hospital and Research Center, Sri Ganganagar 335002, Rajasthan, India
| | - Kiran Lata Sharma
- Department of Pathology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Hu Y, Cao H, Sheng J, Sun Y, Zhu Y, Lin Q, Yi N, He S, Peng L, Li L. Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure. J Genet Genomics 2024; 51:844-854. [PMID: 38575112 DOI: 10.1016/j.jgg.2024.03.010] [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: 12/13/2023] [Revised: 03/25/2024] [Accepted: 03/26/2024] [Indexed: 04/06/2024]
Abstract
Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with noncoding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that cardiac hypertrophy-related circRNA (circRNA CHRC), within the ceRNA network, is down-regulated in both transverse aortic constriction mice and Ang-II--treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and β-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.
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Affiliation(s)
- Yi Hu
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Huaming Cao
- Department of Cardiology, Shanghai Shibei Hospital, Shanghai 200435, China
| | - Jie Sheng
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Yizhuo Sun
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Yuping Zhu
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Qin Lin
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Na Yi
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Siyu He
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China
| | - Luying Peng
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200120, China.
| | - Li Li
- State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Arrhythmias Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Laboratory of Molecular Genetics and Stem Cell Differentiation, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200120, China.
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Liu YB, Wang Q, Song YL, Song XM, Fan YC, Kong L, Zhang JS, Li S, Lv YJ, Li ZY, Dai JY, Qiu ZK. Abnormal phosphorylation / dephosphorylation and Ca 2+ dysfunction in heart failure. Heart Fail Rev 2024; 29:751-768. [PMID: 38498262 DOI: 10.1007/s10741-024-10395-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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/01/2024] [Indexed: 03/20/2024]
Abstract
Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.
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Affiliation(s)
- Yan-Bing Liu
- Interventional Medical Center, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, China
- Medical College, Qingdao University, Qingdao, China
| | - Qian Wang
- Medical College, Qingdao University, Qingdao, China
| | - Yu-Ling Song
- Department of Pediatrics, Huantai County Hospital of Traditional Chinese Medicine, Zibo, China
| | | | - Yu-Chen Fan
- Medical College, Qingdao University, Qingdao, China
| | - Lin Kong
- Medical College, Qingdao University, Qingdao, China
| | | | - Sheng Li
- Medical College, Qingdao University, Qingdao, China
| | - Yi-Ju Lv
- Medical College, Qingdao University, Qingdao, China
| | - Ze-Yang Li
- Medical College, Qingdao University, Qingdao, China
| | - Jing-Yu Dai
- Department of Oncology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, China.
| | - Zhen-Kang Qiu
- Interventional Medical Center, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, China.
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6
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Hu X, Wang S, Zhao H, Wei Y, Duan R, Jiang R, Wu W, Zhao Q, Gong S, Wang L, Liu J, Yuan P. CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells, pulmonary microvascular endothelial cells, and pericytes under hypoxia. Animal Model Exp Med 2024; 7:310-323. [PMID: 37317637 PMCID: PMC11228088 DOI: 10.1002/ame2.12332] [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: 03/17/2023] [Accepted: 05/07/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. METHODS Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real-time polymerase chain reaction, Cell Counting Kit-8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. RESULTS PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA-432-5p (miR-432-5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR-433-3p in PMECs, and upregulate zinc finger AN1-type containing 5 (ZFAND5) expression by targeting miR-3613-5p in PCs. CONCLUSIONS Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs, through the miR-433-3p/MXI1 axis in PMECs, and through the miR-3613-5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.
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Affiliation(s)
- Xiaoyi Hu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shang Wang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hui Zhao
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai, China
| | - Yaqin Wei
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, China
| | - Ruowang Duan
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Rong Jiang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Wenhui Wu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Qinhua Zhao
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Sugang Gong
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Lan Wang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jinming Liu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ping Yuan
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
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Mably JD, Wang DZ. Long non-coding RNAs in cardiac hypertrophy and heart failure: functions, mechanisms and clinical prospects. Nat Rev Cardiol 2024; 21:326-345. [PMID: 37985696 PMCID: PMC11031336 DOI: 10.1038/s41569-023-00952-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/16/2023] [Indexed: 11/22/2023]
Abstract
The surge in reports describing non-coding RNAs (ncRNAs) has focused attention on their possible biological roles and effects on development and disease. ncRNAs have been touted as previously uncharacterized regulators of gene expression and cellular processes, possibly working to fine-tune these functions. The sheer number of ncRNAs identified has outpaced the capacity to characterize each molecule thoroughly and to reliably establish its clinical relevance; it has, nonetheless, created excitement about their potential as molecular targets for novel therapeutic approaches to treat human disease. In this Review, we focus on one category of ncRNAs - long non-coding RNAs - and their expression, functions and molecular mechanisms in cardiac hypertrophy and heart failure. We further discuss the prospects for this specific class of ncRNAs as novel targets for the diagnosis and treatment of these conditions.
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Affiliation(s)
- John D Mably
- Center for Regenerative Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
- USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Da-Zhi Wang
- Center for Regenerative Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
- USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
- Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
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Singh DD, Kim Y, Choi SA, Han I, Yadav DK. Clinical Significance of MicroRNAs, Long Non-Coding RNAs, and CircRNAs in Cardiovascular Diseases. Cells 2023; 12:1629. [PMID: 37371099 DOI: 10.3390/cells12121629] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/17/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.
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Affiliation(s)
- Desh Deepak Singh
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, India
| | - Youngsun Kim
- Department of Obstetrics and Gynecology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Seung Ah Choi
- Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul 08826, Republic of Korea
| | - Ihn Han
- Plasma Bioscience Research Center, Applied Plasma Medicine Center, Department of Plasma Biodisplay, Kwangwoon University, Seoul 01897, Republic of Korea
| | - Dharmendra Kumar Yadav
- Department of Pharmacy, Gachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, Incheon 21924, Republic of Korea
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9
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Wu P, Qin J, Liu L, Tan W, Lei L, Zhu J. circEPSTI1 promotes tumor progression and cisplatin resistance via upregulating MSH2 in cervical cancer. Aging (Albany NY) 2022; 14:5406-5416. [PMID: 35779530 PMCID: PMC9320557 DOI: 10.18632/aging.204152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/01/2022] [Indexed: 02/07/2023]
Abstract
CircRNAs (circRNAs) are a kind of non-coding RNAs which are extensively distributed in tissues. Previous investigations reported that circRNAs harbor indispensable roles in modulating the progress of multiple cancers. Nevertheless, the function along with the molecular mechanism of most circRNAs in cervical cancer progression was still not clear. Herein, we illustrated that circEPSTI1 is a remarkably upregulated circRNA, which we validated in tissues with cervical cancer along with cell lines. The biological role of circEPSTI1 in the advancement of cervical cancer was probed via loss-of function assessments. Silencing circEPSTI1 could diminish the proliferative capacity of the cervical cancer cells to spread. In cervical cancer cells, silencing circEPSTI1 dramatically elevated drug responsivity to cisplatin. Mechanically, RNA immuno-precipitation experiments and dual luciferase enzyme reporter experiments were conducted to reveal the molecular mechanism of circEPSTI1 in cervical cancer. In conclusion, this research premise identified the biological function of circEPSTI1-miR-370-3p-MSH2 axis in cervical cancer progression. Our result is significant for slowing the progress of and overcoming drug resistance of cervical cancer.
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Affiliation(s)
- Peng Wu
- Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China
| | - Jing Qin
- Department of Pathology, The First People's Hospital of Changde City, Changde 415000, China
| | - Lingyan Liu
- Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China
| | - Wupeng Tan
- Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China
| | - Linchen Lei
- Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China
| | - Jiayu Zhu
- Department of Obstetrics and Gynecology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China
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10
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Zhang X, Gao Y, Wu H, Mao Y. Hsa_circ_0003748 promotes disease progression in rheumatic valvular heart disease by sponging miR-577. J Clin Lab Anal 2022; 36:e24487. [PMID: 35535387 PMCID: PMC9169177 DOI: 10.1002/jcla.24487] [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: 04/11/2022] [Revised: 04/27/2022] [Accepted: 04/28/2022] [Indexed: 11/07/2022] Open
Abstract
The diagnosis and treatment of rheumatic valvular heart disease (RVHD) require substantial improvements. Studies found that circular RNAs (circRNAs) are involved in the progression of cardiovascular diseases. We screened target hsa_circ_0003748 by circRNA microarrays uploaded to a database. We used fluorescence in situ hybridization to determine the cellular location of hsa_circ_0003748. A dual-luciferase reporter gene assay revealed that has_circ_0003748 might bind the miRNA miR-577. In hVIC cells (an RVHD cell line), Cell Counting Kit-8, Transwell, and flow cytometry assays measured proliferation, migration, and cell cycle and apoptosis, respectively. We found that hsa_circ_0003748 was localized in the cytoplasm; hsa_circ_0003748 promoted the proliferation and migration of hVIC cells, arrested the cell cycle in the G2/M phase, and inhibited apoptosis. These phenomena may result from hsa_circ_0003748 promoting RVHD after sponging miR-577. Bioinformatic analysis revealed that hsa_circ_0003748 might affect RVHD progression by affecting transcription and the MAPK signaling pathway, the Ras signaling pathway, the cAMP signaling pathway, the Rap1 signaling pathway, and other signaling pathways.
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Affiliation(s)
- Xiaoyun Zhang
- Cardio-vascular Surgery, Ningbo First Hospital, Ningbo, China
| | - Yakun Gao
- Cardio-vascular Surgery, Ningbo First Hospital, Ningbo, China
| | - Hongyu Wu
- Cardio-vascular Surgery, Ningbo First Hospital, Ningbo, China
| | - Yong Mao
- Cardio-vascular Surgery, Ningbo First Hospital, Ningbo, China
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Machine learning approaches to explore digenic inheritance. Trends Genet 2022; 38:1013-1018. [DOI: 10.1016/j.tig.2022.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 04/16/2022] [Accepted: 04/25/2022] [Indexed: 11/22/2022]
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