Open Access

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

  • Authors:
    • Shuwei Ning
    • Zhiying Li
    • Zhenyu Ji
    • Dandan Fan
    • Keke Wang
    • Qian Wang
    • Lei Hua
    • Junyue Zhang
    • Xiangguang Meng
    • Yiqiang Yuan
  • View Affiliations

  • Published online on: October 26, 2020     https://doi.org/10.3892/mmr.2020.11636
  • Pages: 5231-5242
  • Copyright: © Ning et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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December-2020
Volume 22 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ning S, Li Z, Ji Z, Fan D, Wang K, Wang Q, Hua L, Zhang J, Meng X, Yuan Y, Yuan Y, et al: MicroRNA‑494 suppresses hypoxia/reoxygenation‑induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1. Mol Med Rep 22: 5231-5242, 2020.
APA
Ning, S., Li, Z., Ji, Z., Fan, D., Wang, K., Wang, Q. ... Yuan, Y. (2020). MicroRNA‑494 suppresses hypoxia/reoxygenation‑induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1. Molecular Medicine Reports, 22, 5231-5242. https://doi.org/10.3892/mmr.2020.11636
MLA
Ning, S., Li, Z., Ji, Z., Fan, D., Wang, K., Wang, Q., Hua, L., Zhang, J., Meng, X., Yuan, Y."MicroRNA‑494 suppresses hypoxia/reoxygenation‑induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1". Molecular Medicine Reports 22.6 (2020): 5231-5242.
Chicago
Ning, S., Li, Z., Ji, Z., Fan, D., Wang, K., Wang, Q., Hua, L., Zhang, J., Meng, X., Yuan, Y."MicroRNA‑494 suppresses hypoxia/reoxygenation‑induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1". Molecular Medicine Reports 22, no. 6 (2020): 5231-5242. https://doi.org/10.3892/mmr.2020.11636