Pathological cardiac hypertrophy is the leading cause of heart failure, and miRNAs have been recognized as key factors in cardiac hypertrophy. This study aimed to elucidate whether miR-17-5p affects cardiac hypertrophy by targeting the mitochondrial fusion protein mitofusin 2 (Mfn2)-mediated phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and regulating autophagy. miR-17-5p expression was shown to be upregulated both in vivo and in vitro. In addition, a miR-17-5p inhibitor significantly reversed AngII-induced cell hypertrophy in neonatal rat left ventricle myocytes (NRVMs). In contrast to miR-17-5p expression, Mfn2 expression was inhibited in rat hearts at 4 weeks after transverse aortic constriction (TAC) and in an Ang II-induced cell hypertrophy model. We examined miR-17-5p targeting of Mfn2 by dual luciferase reporter and Western blot assays. In addition, we also verified the relationship between Mfn2 and the PI3K/AKT/mTOR pathway. Mfn2 overexpression attenuated miR-17-5p-induced cell hypertrophy, and in rat myocardial tissue, miR-17-5p induced autophagy inhibition. In summary, the results of the present study demonstrated that miR-17-5p inhibits Mfn2 expression, activates the PI3K/AKT/mTOR pathway and suppresses autophagy to promote cardiac hypertrophy.

病理性心脏肥大是心力衰竭的主要原因，miRNA已被认为是心脏肥大的关键因素。本研究旨在阐明miR-17-5p是否通过靶向线粒体融合蛋白线粒体融合蛋白2（Mfn2）介导的磷脂酰肌醇3激酶（PI3K）/AKT/哺乳动物雷帕霉素靶点（mTOR）通路并调节自噬来影响心脏肥大。 miR-17-5p 表达在体内和体外均被上调。此外，miR-17-5p 抑制剂可显着逆转 AngII 诱导的新生大鼠左心室肌细胞 (NRVM) 细胞肥大。与 miR-17-5p 表达相反，横主动脉缩窄 (TAC) 4 周后大鼠心脏中以及 Ang II 诱导的细胞肥大模型中 Mfn2 表达受到抑制。我们通过双荧光素酶报告基因和蛋白质印迹分析检查了 miR-17-5p 对 Mfn2 的靶向作用。此外，我们还验证了Mfn2与PI3K/AKT/mTOR通路的关系。 Mfn2 过表达减弱了 miR-17-5p 诱导的细胞肥大，并且在大鼠心肌组织中，miR-17-5p 诱导自噬抑制。总之，本研究结果表明，miR-17-5p抑制Mfn2表达，激活PI3K/AKT/mTOR通路并抑制自噬促进心脏肥大。