中山大学学报(医学科学版)2017,Vol.38Issue(6):820-826,877,8.
miR-92b-3p靶向肌细胞增强子2D抑制心肌细胞肥大
Targeting Myocyte-specific Enhancer Factor 2D Contributes to the Suppression of Cardiac Hypertrophic Growth by MiR-92b-3p in Cardiomyocytes
摘要
Abstract
[Objective]To investigate the role and the potential target of miR-92b-3p in angiotensin Ⅱ(Ang-Ⅱ)-induced mouse cardiac hypertrophy.[Methods]Ang-Ⅱ-induced cardiac hypertrophy models were established in adult C57BL/6 mice. AgomiR-92b-3p,the cholesterol-modified miR-92b-3p mimic,was delivered to increase the level of miR-92b-3p in mouse myocar?dium via tail vein injection. In the present study,three groups of mice were used in the animal experiment as follows,the agomiR-negative control(agomiR-NC)+saline group,the agomiR-NC+Ang-Ⅱgroup and the agomiR-92b-3p+Ang-Ⅱgroup. A cell model of cardiac hypertrophy was also established in Ang-Ⅱ-induced neonatal mouse cardiomyocytes in this study Luciferase activity was assayed after transfection using a luciferase reporter assay system. The expression of Myocyte-specific enhancer factor 2D( MEF2D) and hypertrophy-related genes atrial natriuretic peptide (ANP),cardiac muscle α-actin (ACTA1) and β-myosin heavy chain (MHC)at mRNA and protein levels in Ang-Ⅱ-induced hypertrophic myocardium and cardiomyocytes were detected by qRT-PCR and Western blot,respectively.[Results]The expression of ANP,ACTA1,β-MHC were markedly increased in Ang-Ⅱ-induced hypertrophic myocardium and cardiomyocytes. Dual luciferase reporter assay revealed that MEF2D is a potential target gene of miR-92b-3p. And miR-92b-3p can reduce the expression of MEF2D at the post-transcriptional level. Functionally,miR-92b-3p mimic, consistent with MEF2D siRNA,inhibited cell size increase and protein expression of ANP,ACTA1 andβ-MHC in Ang-II-treated mouse cardiomyocytes.[Conclusions]MEF2D is a novel target of miR-92b-3p,a target gene of miR-92b-3,which mediates the ef?fect of miR-92b-3p on attenuating cardiomyocyte hypertrophy.关键词
心肌肥厚/microRNA-92b-3p/MEF2DKey words
cardiac hypertrophy/miR-92b-3p/MEF2D分类
医药卫生引用本文复制引用
胡志琴,朱杰宁,杨静,林秋雄,符永恒,张梦珍,吴书林,单志新..miR-92b-3p靶向肌细胞增强子2D抑制心肌细胞肥大[J].中山大学学报(医学科学版),2017,38(6):820-826,877,8.基金项目
国家自然科学基金(91649109,81470439,81770264) (91649109,81470439,81770264)
广东省自然科学基金(2014A030313635,2013B022000083) (2014A030313635,2013B022000083)
广东省医学研究基金(A2015187) (A2015187)