MiRNA‐339‐5p promotes isoproterenol‐induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling

Autor: Xueying Bi, Jiantao Ye, Peiqing Liu, Siting Xu, Fang Liu, Yuhong Zhang, Youhui Yu, Jing Yuan
Rok vydání: 2021
Předmět:
Zdroj: Cell Biology International. 46:288-299
ISSN: 1095-8355
1065-6995
DOI: 10.1002/cbin.11731
Popis: MicroRNAs (miRNAs) regulate multiple biological processes and participate in various cardiovascular diseases. This study aims to investigate the role of miR-339-5p in cardiomyocyte hypertrophy and the involved mechanism. Neonatal rat cardiomyocytes (NRCMs) were cultured and stimulated with isoproterenol (ISO). The hypertrophic responses were monitored by measuring the cell surface area and expression of hypertrophic markers including β-myosin heavy chain (β-MHC) and atrial natriuretic factor (ANF). Bioinformatic prediction tools and dual-luciferase reporter assay were performed to identify the target gene of miR-339-5p. Quantitative real-time polymerase chain reaction and Western blot analysis were used to determine the levels of miR-339-5p and its downstream effectors. Our data showed that miR-339-5p was up-regulated during cardiomyocyte hypertrophy triggered by ISO. MiR-339-5p overexpression resulted in enlargement of cell size and increased the levels of hypertrophic markers. In contrast, inhibition of miR-339-5p significantly attenuated ISO-induced hypertrophic responses of NRCMs. Valosin-containing protein (VCP), a suppressor of cardiac hypertrophy via inhibiting mechanistic target of rapamycin (mTOR) signaling, was validated as a target of miR-339-5p. MiR-339-5p suppressed VCP protein expression, leading to elevated phosphorylation of mTOR and ribosomal protein S6 kinase (S6K). VCP depletion activated the mTOR/S6K cascade and could compromise the anti-hypertrophic effects of miR-339-5p inhibitor. Additionally, the hypertrophic responses caused by miR-339-5p was alleviated in the presence of mTOR inhibitor rapamycin. In conclusion, our research revealed that miR-339-5p promoted ISO-induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling, suggesting a promising therapeutic intervention by interfering miR-339-5p. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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