Targeting myocyte-specific enhancer factor 2D contributes to the suppression of cardiac hypertrophic growth by miR-92b-3p in mice.
Targeting myocyte-specific enhancer factor 2D contributes to the suppression of cardiac hypertrophic growth by miR-92b-3p in mice.
复制标题
靶向心肌细胞特异性增强因子 2D 有助于通过 miR-92b-3p 抑制小鼠心肌肥厚生长
DOI：
10.18632/oncotarget.20759
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Shan ZX
中科院分区：
文献类型：
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作者：
Hu ZQ;Luo JF;Yu XJ;Zhu JN;Huang L;Yang J;Fu YH;Li T;Xue YM;Feng YQ;Shan ZX
MicroRNA-92b-3p(miR-92b-3p)在心肌肥厚中的作用尚不清楚。本研究旨在探讨miR-92b-3p在血管紧张素II(Ang-II)诱导的小鼠心肌肥厚中的表达及其可能的靶点。在Ang-II灌流的小鼠和心肌肥厚患者的心肌中，miR-92b-3p显著降低。然而，在Ang-II诱导的新生小鼠心肌细胞中，miR-92b-3p的表达增加。尾静脉注射模拟血管紧张素Ⅱ的miR-92b-3p后，心肌肥厚明显减轻。此外，miR-92b-3p抑制Ang-II诱导的小鼠心肌细胞心钠素、骨骼肌α-肌动蛋白和β-肌球蛋白重链的表达。心肌细胞特异性增强因子2D(MEF2D)是miR-92b-3p的靶基因，在Ang-II诱导的小鼠肥大心肌和心肌细胞中表达增加。在功能上，miR-92b-3p模拟血管紧张素Ⅱ处理的小鼠心肌细胞，抑制心钠素、ACTA1和β-MHC的蛋白表达，与MEF2DsiRNA一致。综上所述，我们证明MEF2D是miR-92b-3p的一个新靶点，miR-92b-3p表达的减弱可能是心肌肥厚时MEF2D增加的原因之一。
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.