Targeting myocyte-specific enhancer factor 2D contributes to the suppression of cardiac hypertrophic growth by miR-92b-3p in mice.

Zhi-Qin Hu,Yong-Heng Fu,Jian-Fang Luo,Jing Yang,Xue-Ju Yu,Jie-Ning Zhu,Ying-Qing Feng,Zhi-Xin Shan,Yu-Mei Xue,Tao Li,Lei Huang

doi:10.18632/oncotarget.20759

Abstract

The role of microRNA-92b-3p (miR-92b-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-92b-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. MiR-92b-3p was markedly decreased in the myocardium of Ang-II-infused mice and of patients with cardiac hypertrophy. However, miR-92b-3p expression was revealed increased in Ang-II-induced neonatal mouse cardiomyocytes. Cardiac hypertrophy was shown attenuated in Ang-II-infused mice received tail vein injection of miR-92b-3p mimic. Moreover, miR-92b-3p inhibited the expression of atrial natriuretic peptide (ANP), skeletal muscle α-actin (ACTA1) and β-myosin heavy chain (MHC) in Ang-II-induced mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2D (MEF2D), which was increased in Ang-II-induced mouse hypertrophic myocardium and cardiomyocytes, was identified as a target gene of miR-92b-3p. Functionally, miR-92b-3p mimic, consistent with MEF2D siRNA, inhibited cell size increase and protein expression of ANP, ACTA1 and β-MHC in Ang-II-treated mouse cardiomyocytes. Taken together, we demonstrated that MEF2D is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression may contribute to the increase of MEF2D in cardiac hypertrophy.

Highlights

Hypertension, genetic polymorphisms, loss of cardiomyocytes following ischaemic damage and altered cardiac metabolism are known as the main causes of pathological cardiac hypertrophy [1, 2]
We demonstrated that Myocyte-specific enhancer factor 2D (MEF2D) is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression may contribute to the increase of MEF2D in cardiac hypertrophy
Results of Western-blotting showed that the hypertrophyassociated genes, including atrial natriuretic peptide (ANP), ACTA1 and β-myosin heavy chain (MHC), were significantly increased in mouse myocardium subjected to angiotensin II (Ang-II) treatment (Figure 1D)

Summary

Introduction

Hypertension, genetic polymorphisms, loss of cardiomyocytes following ischaemic damage and altered cardiac metabolism are known as the main causes of pathological cardiac hypertrophy [1, 2]. At the early stage of pathological hypertrophy, the increased size of cardiomyocytes is initially a compensatory mechanism, the sustained hypertrophy may eventually lead to dilated cardiomyopathy, arrhythmia, heart failure and even sudden death [3,4,5]. No efficient therapeutic approaches are available for the treatment of cardiac hypertrophy. MicroRNA-1, -16 and microRNA-181b were downregulated in cardiac hypertrophy, and in vitro over-expression of them resulted in the reduced size of cardiomyocytes [7,8,9]. MicroRNA-208a and microRNA-195 were up-regulated in cardiac hypertrophy, which were sufficient to drive pathological cardiac growth when over-expressed in transgenic mice, respectively [10, 11]

Methods

Results

Conclusion