MicroRNA‑494 suppresses hypoxia/reoxygenation‑induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1.

Content Provider	Europe PMC
Author	Ning, Shuwei Li, Zhiying Ji, Zhenyu Fan, Dandan Wang, Keke Wang, Qian Hua, Lei Zhang, Junyue Meng, Xiangguang Yuan, Yiqiang
Copyright Year	2020
Abstract	Acute myocardial infarction can be caused by ischemia/reperfusion (I/R) injury; however, the mechanism underlying I/R is not completely understood. The present study investigated the functions and mechanisms underlying microRNA (miR)-494 in I/R-induced cardiomyocyte apoptosis and autophagy. Hypoxia/reoxygenation (H/R)-treated H9c2 rat myocardial cells were used as an in vitro I/R injury model. Apoptosis and autophagy were analyzed by Cell Counting Kit-8 assay, Lactic dehydrogenase and superoxide dismutase assay, flow cytometry, TUNEL staining and western blotting. Reverse transcription-quantitative PCR demonstrated that, H9c2 cells treated with 12 h hypoxia and 3 h reoxygenation displayed significantly downregulated miR-494 expression levels compared with control cells. Compared with the corresponding negative control (NC) groups, miR-494 mimic reduced H/R-induced cell apoptosis and autophagy, whereas miR-494 inhibitor displayed the opposite effects. Silent information regulator 1 (SIRT1) was identified as a target gene of miR-494. Furthermore, miR-494 inhibitor-mediated effects on H/R-induced cardiomyocyte apoptosis and autophagy were partially reversed by SIRT1 knockdown. Moreover, compared with si-NC, SIRT1 knockdown significantly increased the phosphorylation levels of PI3K, AKT and mTOR in H/R-treated and miR-494 inhibitor-transfected H9c2 cells. Collectively, the results indicated that miR-494 served a protective role against H/R-induced cardiomyocyte apoptosis and autophagy by directly targeting SIRT1, suggesting that miR-494 may serve as a novel therapeutic target for myocardial I/R injury.
ISSN	17912997
Journal	Molecular Medicine Reports
Volume Number	22
PubMed Central reference number	PMC7646990
Issue Number	6
PubMed reference number	33174056
e-ISSN	17913004
DOI	10.3892/mmr.2020.11636
Language	English
Publisher	D.A. Spandidos
Publisher Date	2020-10-26
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Ning et al.
Subject Keyword	miR-494 myocardial I/R injury SIRT1 apoptosis autophagy PI3K/AKT/mTOR signaling pathway
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Biochemistry Cancer Research Molecular Medicine Oncology