Hu Zhi-Qin, Luo Jian-Fang, Yu Xue-Ju, Zhu Jie-Ning, Huang Lei, Yang Jing, Fu Yong-Heng, Li Tao, Xue Yu-Mei, Feng Ying-Qing, Shan Zhi-Xin
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Oncotarget. 2017 Sep 8;8(54):92079-92089. doi: 10.18632/oncotarget.20759. eCollection 2017 Nov 3.
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 . 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.
微小RNA-92b-3p(miR-92b-3p)在心肌肥大中的作用尚未得到充分阐明。本研究旨在探讨miR-92b-3p在血管紧张素II(Ang-II)诱导的小鼠心肌肥大中的表达及潜在靶点。在Ang-II灌注小鼠和心肌肥大患者的心肌中,miR-92b-3p明显降低。然而,在Ang-II诱导的新生小鼠心肌细胞中,miR-92b-3p表达增加。尾静脉注射miR-92b-3p模拟物的Ang-II灌注小鼠的心肌肥大减轻。此外,miR-92b-3p抑制了Ang-II诱导的小鼠心肌细胞中的心钠素(ANP)、骨骼肌α-肌动蛋白(ACTA1)和β-肌球蛋白重链(MHC)的表达。肌细胞特异性增强因子2D(MEF2D)在Ang-II诱导的小鼠肥厚心肌和心肌细胞中增加,被确定为miR-92b-3p的靶基因。在功能上,miR-92b-3p模拟物与MEF2D小干扰RNA一致,抑制了Ang-II处理的小鼠心肌细胞的细胞大小增加以及ANP、ACTA1和β-MHC的蛋白表达。综上所述,我们证明MEF2D是miR-92b-3p的新靶点,miR-92b-3p表达的减弱可能导致心肌肥大中MEF2D的增加。