Expression Profile of microRNAs in Hypertrophic Cardiomyopathy and Effects of microRNA-20 in Inducing Cardiomyocyte Hypertrophy Through Regulating Gene MFN2
机构：[1]Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.临床科室高血压科首都医科大学附属安贞医院[2]Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.首都医科大学附属安贞医院[3]Beijing Laboratory for Cardiovascular Precision Medicine (PXM2017_014226_000037), Beijing, China
Myocardial hypertrophy is an important cause of heart failure and sudden death. Studies have shown that Mitofusin-2 (MFN2) is downregulated in myocardial hypertrophy, but the upstream regulation mechanism underlying its downexpression in cardiomyocytes is still unclear. This study aims to identify the expression profile of microRNAs (miRNAs) in hypertrophic cardiomyopathy (HCM) and explore the function of miRNA-20 in inducing cardiomyocyte hypertrophy through regulating MFN2. Through miRNA + mRNA microarray analysis, 1451 miRNAs were identified, 367 miRNAs expressed differently between groups. Meanwhile, a number of 24,718 mRNAs were identified, among which 5850 mRNAs were upregulated and 3005 mRNAs were downregulated in HCM group compared with the control group. Expression of hsa-miRNA-20a-5p was 2.26 times higher in the HCM group compared with the control group and 7 target gene prediction programs predicted MFN2 as a target of miRNA-20. In vitro model of hypertrophic cardiomyocytes displayed high expression level of miRNA-20, atrial natriuretic peptide (ANP) mRNA, and protein, accompanying low expression level of Mfn2 mRNA and protein, which meant miRNA-20 played a role in cardiomyocyte hypertrophy and might interact with MFN2 to function. Thereafter, overexpression of miRNA-20 led to cell hypertrophy accompanied with lowly expressed Mfn2 mRNA and protein. When transfected with miRNA-20 inhibitors, the expression of miRNA-20 and ANP gene was attenuated and MFN2 was the other way around. The cell surface area of Ang II group and mimic group was significantly larger compared with the control group, and in the inhibitor+Ang II group, the area was significantly decreased compared with the Ang II group. Dual-luciferase assays showed that miRNA-20 bound to 3 ' untranslated region of MFN2 and inhibited its expression. In conclusion, hypertrophic myocardium and normal myocardium have different miRNA expression profiles and the effect of miRNA-20 reducing the expression of MFN2 plays a role in promoting cardiomyocyte hypertrophy.
基金：
Beijing Natural Science FoundationBeijing Natural Science Foundation [7120001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81370229, 81270216]
第一作者机构：[1]Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.[2]Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.[3]Beijing Laboratory for Cardiovascular Precision Medicine (PXM2017_014226_000037), Beijing, China
通讯作者：
通讯机构：[1]Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.[2]Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.[3]Beijing Laboratory for Cardiovascular Precision Medicine (PXM2017_014226_000037), Beijing, China[*1]Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
推荐引用方式(GB/T 7714)：
Sun Dongdong,Li Chuang,Liu Jielin,et al.Expression Profile of microRNAs in Hypertrophic Cardiomyopathy and Effects of microRNA-20 in Inducing Cardiomyocyte Hypertrophy Through Regulating Gene MFN2[J].DNA AND CELL BIOLOGY.2019,38(8):796-807.doi:10.1089/dna.2019.4731.
APA：
Sun, Dongdong,Li, Chuang,Liu, Jielin,Wang, Zuoguang,Liu, Ya...&Wen, Shaojun.(2019).Expression Profile of microRNAs in Hypertrophic Cardiomyopathy and Effects of microRNA-20 in Inducing Cardiomyocyte Hypertrophy Through Regulating Gene MFN2.DNA AND CELL BIOLOGY,38,(8)
MLA：
Sun, Dongdong,et al."Expression Profile of microRNAs in Hypertrophic Cardiomyopathy and Effects of microRNA-20 in Inducing Cardiomyocyte Hypertrophy Through Regulating Gene MFN2".DNA AND CELL BIOLOGY 38..8(2019):796-807
