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

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.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Yang Y,Ding S,Xu G,Chen F,Ding F

doi

10.3892/mmr.2017.6466

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

3699-3705

issue

6

eissn

1791-2997

issn

1791-3004

journal_volume

15

pub_type

杂志文章

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