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MicroRNA-17-5p Promotes Cardiac Hypertrophy by Targeting Mfn2 to Inhibit Autophagy

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Abstract

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.

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Acknowledgements

This work was supported by The Six Talent Peaks Project in Jiangsu Province, China (No. 2016-WSN-103) and the Nantong Science and Technology Bureau, China (No. JC2018082; MS22018005).

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    1. Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Xuan Xu, Yi-ling Su, Jia-yu Shi, Qi Lu & Chu Chen

    2. Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China

      Xuan Xu

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    Xu, X., Su, Yl., Shi, Jy. et al. MicroRNA-17-5p Promotes Cardiac Hypertrophy by Targeting Mfn2 to Inhibit Autophagy. Cardiovasc Toxicol 21, 759–771 (2021). https://doi.org/10.1007/s12012-021-09667-w

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