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This study aims to investigate the role of miR\u2010339\u20105p 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 \u03b2\u2010myosin heavy chain (\u03b2\u2010MHC) and atrial natriuretic factor (ANF). Bioinformatic prediction tools and dual\u2010luciferase reporter assay were performed to identify the target gene of miR\u2010339\u20105p. Quantitative real\u2010time polymerase chain reaction and western blot analysis were used to determine the levels of miR\u2010339\u20105p and its downstream effectors. Our data showed that miR\u2010339\u20105p was upregulated during cardiomyocyte hypertrophy triggered by ISO. MiR\u2010339\u20105p overexpression resulted in enlargement of cell size and increased the levels of hypertrophic markers. In contrast, inhibition of miR\u2010339\u20105p significantly attenuated ISO\u2010induced hypertrophic responses of NRCMs. Valosin\u2010containing protein (VCP), a suppressor of cardiac hypertrophy via inhibiting mechanistic target of rapamycin (mTOR) signaling, was validated as a target of miR\u2010339\u20105p. MiR\u2010339\u20105p 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\u2010hypertrophic effects of miR\u2010339\u20105p inhibitor. Additionally, the hypertrophic responses caused by miR\u2010339\u20105p was alleviated in the presence of mTOR inhibitor rapamycin. In conclusion, our research revealed that miR\u2010339\u20105p promoted ISO\u2010induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling, suggesting a promising therapeutic intervention by interfering miR\u2010339\u20105p.<\/jats:p>","DOI":"10.1002\/cbin.11731","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T13:48:34Z","timestamp":1638452914000},"page":"288-299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MiRNA\u2010339\u20105p promotes isoproterenol\u2010induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling"],"prefix":"10.1002","volume":"46","author":[{"given":"Xueying","family":"Bi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Sun Yat\u2010Sen University Guangdong Guangzhou 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