Targeting Myocyte-specific Enhancer Factor 2D Contributes to the Suppression of Cardiac Hypertrophic Growth by MiR-92b-3p in Cardiomyocytes
- VernacularTitle:miR-92b-3p靶向肌细胞增强子2D抑制心肌细胞肥大
- Author:
qin Zhi HU
1
;
ning Jie ZHU
;
Jing YANG
;
xiong Qiu LIN
;
heng Yong FU
;
zhen Meng ZHANG
;
lin Shu WU
;
xin Zhi SHAN
Author Information
1. 南方医科大学药学院
- Keywords:
cardiac hypertrophy;
miR-92b-3p;
MEF2D
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2017;38(6):820-826,877
- CountryChina
- Language:Chinese
-
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.