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Pasławska M, Grodzka A, Peczyńska J, Sawicka B, Bossowski AT. Role of miRNA in Cardiovascular Diseases in Children-Systematic Review. Int J Mol Sci 2024; 25:956. [PMID: 38256030 PMCID: PMC10816020 DOI: 10.3390/ijms25020956] [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: 11/18/2023] [Revised: 12/26/2023] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.
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Affiliation(s)
| | | | | | | | - Artur Tadeusz Bossowski
- Department of Pediatrics, Endocrinology, Diabetology with Cardiology Divisions, Medical University of Bialystok, J. Waszyngtona 17, 15-274 Bialystok, Poland; (M.P.); (A.G.); (J.P.); (B.S.)
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2
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Actin-Binding Proteins in Cardiac Hypertrophy. Cells 2022; 11:cells11223566. [PMID: 36428995 PMCID: PMC9688942 DOI: 10.3390/cells11223566] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/04/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
The heart reacts to a large number of pathological stimuli through cardiac hypertrophy, which finally can lead to heart failure. However, the molecular mechanisms of cardiac hypertrophy remain elusive. Actin participates in the formation of highly differentiated myofibrils under the regulation of actin-binding proteins (ABPs), which provides a structural basis for the contractile function and morphological change in cardiomyocytes. Previous studies have shown that the functional abnormality of ABPs can contribute to cardiac hypertrophy. Here, we review the function of various actin-binding proteins associated with the development of cardiac hypertrophy, which provides more references for the prevention and treatment of cardiomyopathy.
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Hailu FT, Karimpour-Fard A, Toni LS, Bristow MR, Miyamoto SD, Stauffer BL, Sucharov CC. Integrated analysis of miRNA-mRNA interaction in pediatric dilated cardiomyopathy. Pediatr Res 2022; 92:98-108. [PMID: 34012027 PMCID: PMC8602449 DOI: 10.1038/s41390-021-01548-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 03/10/2021] [Accepted: 04/08/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND MicroRNAs (miRNAs) are short single-stranded nucleotides that can regulate gene expression. Although we previously evaluated the expression of miRNAs in pediatric dilated cardiomyopathy (DCM) by miRNA array, pathway prediction based on changes in mRNA expression has not been previously analyzed in this population. The current study aimed to determine the regulation of miRNA expression by miRNA-sequencing (miRNA-seq) and, through miRNA-sequencing (mRNA-seq), analyze their putative target genes and altered pathways in pediatric DCM hearts. METHODS miRNA expression was determined by miRNA-seq [n = 10 non-failing (NF), n = 20 DCM]. Expression of a subset of miRNAs was evaluated in adult DCM patients (n = 11 NF, n = 13 DCM). miRNA-mRNA prediction analysis was performed using mRNA-seq data (n = 7 NF, n = 7 DCM) from matched samples. RESULTS Expression of 393 miRNAs was significantly different (p < 0.05) in pediatric DCM patients compared to NF controls. TargetScan-based miRNA-mRNA analysis revealed 808 significantly inversely expressed genes. Functional analysis suggests upregulated pathways related to the regulation of stem cell differentiation and cardiac muscle contraction, and downregulated pathways related to the regulation of protein phosphorylation, signal transduction, and cell communication. CONCLUSIONS Our results demonstrated a unique age-dependent regulation of miRNAs and their putative target genes, which may contribute to distinctive phenotypic characteristics of DCM in children. IMPACT This is the first study to compare miRNA expression in the heart of pediatric DCM patients to age-matched healthy controls by RNA sequencing. Expression of a subset of miRNAs is uniquely dysregulated in children. Using mRNA-seq and miRNA-seq from matched samples, target prediction was performed. This study underscores the importance of pediatric-focused studies.
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Affiliation(s)
- Frehiwet T Hailu
- Department of Medicine/Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA
| | | | - Lee S Toni
- Department of Medicine/Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Michael R Bristow
- Department of Medicine/Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Shelley D Miyamoto
- Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Brian L Stauffer
- Department of Medicine/Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
- Division of Cardiology, Denver Health and Hospital Authority, Denver, CO, USA.
| | - Carmen C Sucharov
- Department of Medicine/Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.
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Eyyupkoca F, Ercan K, Kiziltunc E, Ugurlu IB, Kocak A, Eyerci N. Determination of microRNAs associated with adverse left ventricular remodeling after myocardial infarction. Mol Cell Biochem 2022; 477:781-791. [PMID: 35048282 DOI: 10.1007/s11010-021-04330-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 12/09/2021] [Indexed: 12/22/2022]
Abstract
Increasing evidence indicates that microRNA (miRNA) regulated mechanisms in myocardial healing and ventricular remodeling following acute myocardial infarction (AMI). We aim to comprehensively investigate changes of exosomal miRNA profile during the post-MI period and determine potential miRNAs associated to adverse left ventricular remodeling (ALVR). We prospectively evaluated ST-elevated MI patients with cardiac magnetic resonance imaging at the 2 weeks and 6 months after AMI (n = 10). ALVR was defined as an increase in LV end-diastolic and end-systolic volume > 13%. The blood samples were taken for miRNA measurements at the baseline, 2 and 6 weeks after AMI. In the miRNA profile assessment, 8 miRNAs were identified that were associated ALVR (miR-199a-5p, miR-23b-3p, miR-26b-5p, miR-301a-3p, miR-374a-5p, miR-423-5p, miR-483-5p and miR-652-3p). Three of them (miR-301a-3p, miR-374a-5p and miR-423-5p) differed significantly between patients with and without ALVR during follow-up period and the rest of them during the acute phase of AMI. The detection of these miRNAs, which have different role in various pathways, necessitate future mechanistic studies unravel the complex remodeling process after AMI.
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Affiliation(s)
- Ferhat Eyyupkoca
- Department of Cardiology, Dr. Nafiz Korez Sincan State Hospital, Fatih District, Gazi Mustafa Kemal Boulevard, 06930, Ankara, Turkey.
| | - Karabekir Ercan
- Department of Radiology, Ankara City Hospital, Ankara, Turkey
| | - Emrullah Kiziltunc
- Department of Cardiology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Ilgin Burcu Ugurlu
- Department of Cardiology, Gulhane Training and Research Hospital, Ankara, Turkey
| | - Ajar Kocak
- Department of Cardiology, Dr. Nafiz Korez Sincan State Hospital, Fatih District, Gazi Mustafa Kemal Boulevard, 06930, Ankara, Turkey
| | - Nilnur Eyerci
- Department of Medical Biology, Kafkas University Faculty of Medicine, Kars, Turkey
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In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes. Commun Biol 2021; 4:1146. [PMID: 34593953 PMCID: PMC8484596 DOI: 10.1038/s42003-021-02677-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/15/2021] [Indexed: 02/08/2023] Open
Abstract
miRNAs modulate cardiomyocyte specification by targeting mRNAs of cell cycle regulators and acting in cardiac muscle lineage gene regulatory loops. It is unknown if or to-what-extent these miRNA/mRNA networks are operative during cardiomyocyte differentiation of adult cardiac stem/progenitor cells (CSCs). Clonally-derived mouse CSCs differentiated into contracting cardiomyocytes in vitro (iCMs). Comparison of "CSCs vs. iCMs" mRNome and microRNome showed a balanced up-regulation of CM-related mRNAs together with a down-regulation of cell cycle and DNA replication mRNAs. The down-regulation of cell cycle genes and the up-regulation of the mature myofilament genes in iCMs reached intermediate levels between those of fetal and neonatal cardiomyocytes. Cardiomyo-miRs were up-regulated in iCMs. The specific networks of miRNA/mRNAs operative in iCMs closely resembled those of adult CMs (aCMs). miR-1 and miR-499 enhanced myogenic commitment toward terminal differentiation of iCMs. In conclusions, CSC specification/differentiation into contracting iCMs follows known cardiomyo-MiR-dependent developmental cardiomyocyte differentiation trajectories and iCMs transcriptome/miRNome resembles that of CMs.
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Zhen LX, Gu YY, Zhao Q, Zhu HF, Lv JH, Li SJ, Xu Z, Li L, Yu ZR. MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes. World J Stem Cells 2019; 11:1130-1141. [PMID: 31875873 PMCID: PMC6904867 DOI: 10.4252/wjsc.v11.i12.1130] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 09/23/2019] [Accepted: 10/14/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cardiovascular disease is the leading cause of death worldwide. Tissue repair after pathological injury in the heart remains a major challenge due to the limited regenerative ability of cardiomyocytes in adults. Stem cell-derived cardiomyocytes provide a promising source for the cell transplantation-based treatment of injured hearts. AIM To explore the function and mechanisms of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem (mES) cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells. METHODS mES cells with or without overexpression of miR-301a were applied for all functional assays. The hanging drop technique was applied to form embryoid bodies from mES cells. Cardiac markers including GATA-4, TBX5, MEF2C, and α-actinin were used to determine cardiomyocyte differentiation from mES cells. RESULTS High expression of miR-301a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mES cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN is a target gene of miR-301a in cardiomyocytes. PTEN-regulated PI3K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301a-promoted cardiomyocyte differentiation from mES cells. CONCLUSION MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.
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Affiliation(s)
- Li-Xiao Zhen
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Yu-Ying Gu
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Qian Zhao
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Hui-Fang Zhu
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
| | - Jin-Hui Lv
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Shu-Jun Li
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Zhen Xu
- Department of Microbiology and Immunology, Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China
| | - Li Li
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Zuo-Ren Yu
- Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
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7
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Exosomal miR-301 derived from mesenchymal stem cells protects myocardial infarction by inhibiting myocardial autophagy. Biochem Biophys Res Commun 2019; 514:323-328. [PMID: 31036323 DOI: 10.1016/j.bbrc.2019.04.138] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 04/18/2019] [Indexed: 11/23/2022]
Abstract
PURPOSE To investigate the protective effects of miR-301 in exosomes secreted by bone mesenchymal stem cells (BMSCs) on rats' myocardial infarction (MI). METHODS After isolation and culture, BMSCs were identified using flow cytometry. Then exosomes were then isolated. Rats MI models were established and they were divided into 4 groups: Sham group, Model group (injected with PBS), BMSC-Exos group (injected with exosomes secreted by BMSCs), BMSC-301-Exos group (injected with exosomes secreted by BMSCs transfected with miR-301 mimics). Cardiac function was assessed by cardiac echocardiography. Myocardial infarct area was measured by Masson trichrome staining mRNA and proteins expression were measured by qRT-PCR and western blot. Exosome morphology and myocardial cells autophagy were observed by transmission electron microscopy. RESULTS BMSCs were obtained. Rat MI models were successfully established. After rats were injected with exosomes secreted by BMSCs transfected with miR-301 mimics, MI tissues were found to have much higher miR-301 expression, LVEF, LVFS, P62 expression, and remarkably lower LVESD, LVEDD, MI area, LC3-II/LC3-I ratio and autophagosomes numbers compared with BMSC-Exos group (all P < 0.05). CONCLUSION miR-301 in exosomes secreted by BMSCs protected MI by inhibiting myocardial autophagy.
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Huang YM, Li WW, Wu J, Han M, Li BH. The diagnostic value of circulating microRNAs in heart failure. Exp Ther Med 2019; 17:1985-2003. [PMID: 30783473 PMCID: PMC6364251 DOI: 10.3892/etm.2019.7177] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Accepted: 01/07/2019] [Indexed: 12/17/2022] Open
Abstract
Heart failure (HF) is a complex clinical syndrome, characterized by inadequate blood perfusion of tissues and organs caused by decreased heart ejection capacity resulting from structural or functional cardiac disorders. HF is the most severe heart condition and it severely compromises human health; thus, its early diagnosis and effective management are crucial. However, given the lack of satisfactory sensitivity and specificity of the currently available biomarkers, the majority of patients with HF are not diagnosed early and do not receive timely treatment. A number of studies have demonstrated that peripheral blood circulating nucleic acids [such as microRNAs (miRs), mRNA and DNA] are important for the diagnosis and monitoring of treatment response in HF. miRs have been attracting increasing attention as promising biomarkers, given their presence in body fluids and relative structural stability under diverse conditions of sampling. The aim of the present review was to analyze the associations between the mechanisms underlying the development of HF and the expression of miRs, and discuss the value of using circulating miRs as diagnostic biomarkers in HF management. In particular, miR-155, miR-22 and miR-133 appear to be promising for the diagnosis, prognosis and management of HF patients.
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Affiliation(s)
- Yao-Meng Huang
- Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Wei-Wei Li
- Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Jun Wu
- Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Mei Han
- Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
| | - Bing-Hui Li
- Department of Oncological Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
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Onrat ST, Onrat E, Ercan Onay E, Yalım Z, Avşar A. The Genetic Determination of the Differentiation Between Ischemic Dilated Cardiomyopathy and Idiopathic Dilated Cardiomyopathy. Genet Test Mol Biomarkers 2018; 22:644-651. [DOI: 10.1089/gtmb.2018.0188] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Serap Tutgun Onrat
- Department of Medical Genetics, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | - Ersel Onrat
- Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | | | - Zafer Yalım
- Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | - Alaettin Avşar
- Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
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10
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Ehler E. Actin-associated proteins and cardiomyopathy-the 'unknown' beyond troponin and tropomyosin. Biophys Rev 2018; 10:1121-1128. [PMID: 29869751 PMCID: PMC6082317 DOI: 10.1007/s12551-018-0428-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 05/18/2018] [Indexed: 02/06/2023] Open
Abstract
It has been known for several decades that mutations in genes that encode for proteins involved in the control of actomyosin interactions such as the troponin complex, tropomyosin and MYBP-C and thus regulate contraction can lead to hereditary hypertrophic cardiomyopathy. In recent years, it has become apparent that actin-binding proteins not directly involved in the regulation of contraction also can exhibit changed expression levels, show altered subcellular localisation or bear mutations that might lead to hereditary cardiomyopathies. The aim of this review is to look beyond the troponin/tropomyosin mechanism and to give an overview of the different types of actin-associated proteins and their potential roles in cardiomyocytes. It will then discuss recent findings relevant to their involvement in heart disease.
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Affiliation(s)
- Elisabeth Ehler
- Randall Centre for Cell and Molecular Biophysics (School of Basic and Medical Biosciences), London, UK. .,School of Cardiovascular Medicine and Sciences, British Heart Foundation Research Excellence Centre, King's College London, Room 3.26A, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
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Zebrafish VCAP1X2 regulates cardiac contractility and proliferation of cardiomyocytes and epicardial cells. Sci Rep 2018; 8:7856. [PMID: 29777134 PMCID: PMC5959901 DOI: 10.1038/s41598-018-26110-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 05/01/2018] [Indexed: 01/08/2023] Open
Abstract
Sarcomeric signaling complexes are important to sustain proper sarcomere structure and function, however, the mechanisms underlying these processes are not fully elucidated. In a gene trap experiment, we found that vascular cell adhesion protein 1 isoform X2 (VCAP1X2) mutant embryos displayed a dilated cardiomyopathy phenotype, including reduced cardiac contractility, enlarged ventricular chamber and thinned ventricular compact layer. Cardiomyocyte and epicardial cell proliferation was decreased in the mutant heart ventricle, as was the expression of pAKT and pERK. Contractile dysfunction in the mutant was caused by sarcomeric disorganization, including sparse myofilament, blurred Z-disc, and decreased gene expression for sarcomere modulators (smyd1b, mypn and fhl2a), sarcomeric proteins (myh6, myh7, vmhcl and tnnt2a) and calcium regulators (ryr2b and slc8a1a). Treatment of PI3K activator restored Z-disc alignment while injection of smyd1b mRNA restored Z-disc alignment, contractile function and cardiomyocyte proliferation in ventricles of VCAP1X2 mutant embryos. Furthermore, injection of VCAP1X2 variant mRNA rescued all phenotypes, so long as two cytosolic tyrosines were left intact. Our results reveal two tyrosine residues located in the VCAP1X2 cytoplasmic domain are essential to regulate cardiac contractility and the proliferation of ventricular cardiomyocytes and epicardial cells through modulating pAKT and pERK expression levels.
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12
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Zhou G, Li C, Feng J, Zhang J, Fang Y. lncRNA UCA1 Is a Novel Regulator in Cardiomyocyte Hypertrophy through Targeting the miR-184/HOXA9 Axis. Cardiorenal Med 2018; 8:130-139. [PMID: 29616999 DOI: 10.1159/000487204] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 01/24/2018] [Indexed: 01/12/2023] Open
Abstract
Cardiac hypertrophy is closely associated with a series of cardiovascular diseases, including heart failure and sudden death in particular. An in-depth comprehension of the pathogenesis of cardiac hypertrophy will improve the diagnosis and therapy of cardiac hypertrophy. It has been acknowledged that long noncoding RNAs/microRNAs (lncRNAs/miRNAs) are crucial regulators in diverse biological processes, including various cardiovascular diseases, in multiple manners. Nevertheless, the biological roles of lncRNA UCA1 and miR-184 in cardiac hypertrophy are scarcely reported. In this paper, qRT-PCR analysis exhibited that lncRNA UCA1 was highly expressed in mice heart treated with transverse aortic constriction (TAC) and the cardiomyocytes treated with phenylephrine (PE). On the contrary, miR-184 was downregulated under the same conditions. In addition, it was deduced that lncRNA UCA1 was reversely related with miR-184 in PE-triggered hypertrophic cardiomyocytes, confirmed by the Spearman correlation analysis. The knockdown of UCA1 or the overexpression of miR-184 lessened the enlarged surface area of cardiomyocytes and the elevated expressions of fetal genes (ANP and BNP) induced by PE. Later, it was determined that miR-184 was a direct target of UCA1, whereas the mRNA HOXA9 was a target of miR-184. Rescue assays indicated that UCA1 promoted the progression of cardiac hypertrophy through competitively binding with miR-184 to enhance the expression of HOXA9.
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MESH Headings
- Animals
- Blotting, Western
- Cardiomyopathy, Hypertrophic/genetics
- Cardiomyopathy, Hypertrophic/metabolism
- Cardiomyopathy, Hypertrophic/pathology
- Cells, Cultured
- Disease Models, Animal
- Gene Expression Regulation
- Homeodomain Proteins/metabolism
- Male
- Mice
- Mice, Inbred C57BL
- MicroRNAs/metabolism
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- RNA, Long Noncoding/biosynthesis
- RNA, Long Noncoding/genetics
- Real-Time Polymerase Chain Reaction
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