MicroRNA-15a inhibition protects against hypoxia/reoxygenation-induced apoptosis of cardiomyocytes by targeting mothers against decapentaplegic homolog 7

Yang,Yang; Ding,Shiao; Xu,Gaojun; Chen,Fei; Ding,Fangbao

doi:10.3892/mmr.2017.6466

MicroRNA-15a inhibition protects against hypoxia/reoxygenation-induced apoptosis of cardiomyocytes by targeting mothers against decapentaplegic homolog 7

Authors:
- Yang Yang
- Shiao Ding
- Gaojun Xu
- Fei Chen
- Fangbao Ding
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Affiliations: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China
Published online on: April 12, 2017 https://doi.org/10.3892/mmr.2017.6466
Pages: 3699-3705
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial ischemia/reperfusion (I/R) injury is a major pathological process in coronary heart disease and cardiac surgery, and is associated with aberrant microRNA (miR) expression. Previous studies have demonstrated that inhibition of miR-15a expression may ameliorate I/R‑induced myocardial injury. In the present study, the potential role and underlying mechanism of miR‑15a in hypoxia/reoxygenation‑induced apoptosis of cardiomyocytes was investigated. Myocardial I/R was simulated in cultured H9c2 cells by 24 h hypoxia followed by 24 h reoxygenation. Using recombinant lentivirus vectors, the inhibition of miR‑15a was indicated to significantly reduce cardiomyocyte apoptosis and release of lactate dehydrogenase and malondialdehyde. Conversely, upregulated miR‑15a expression was pro‑apoptotic. Mothers against decapentaplegic homolog 7 (SMAD7) was identified by bioinformatics analysis as a potential target of miR‑15a. Luciferase reporter assays and western blotting for endogenous SMAD7 protein indicated that miR‑15a inhibited SMAD7 expression via its 3'‑untranslated region. Nuclear levels of nuclear factor‑κB (NF‑κB) p65 were increased by miR‑15a expression and decreased by miR‑15a inhibition, which is consistent with the possibility that the inhibition of SMAD7 by miR-15a results in NF‑κB activation. These findings suggested that the therapeutic effects of miR‑15a inhibition on I/R injury may potentially be explained by its ability to release SMAD‑7‑dependent NF‑κB inhibition. This may provide evidence for miR‑15a as a potential therapeutic target for the treatment of cardiac I/R injury.

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