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.

Withdrawn: MicroRNA‐142‐5p inhibits autophagy in cardiomyocytes in a mouse model of hypoxia/reoxygenation

“…Previous study [19] shows that miR-142-3p targets box 1, attenuating apoptosis of cardiomyocytes induced by H/R. Research indicates that miRNA-15a targeting mothers against decapentaplegic homolog 7 to protect cardiomyocytes against H/R [20]. R Xu et al [21] reports that miR-142-5p may be involved in the development of atherosclerosis acting with the apoptosis of macrophages.…”

Long non‑coding RNA SNHG16 inhibits the oxygen‑glucose deprivation and reoxygenation‑induced apoptosis in human brain microvascular endothelial cells by regulating miR‑15a‑5p/bcl‑2

“…Previous studies have demonstrated that mir-15a-5p regulates endothelial cell apoptosis during i/r injury (11,30). i/r-induced apoptosis of cardiomyocytes can be promoted by mir-15a-5p by targeting mothers against decapentaplegic homolog 7; inhibition of mir-15a-5p has the opposite effect (30).…”

miR‑15a represses cancer cell migration and invasion under conditions of hypoxia by targeting and downregulating Bcl‑2 expression in human osteosarcoma cells

“…Recent studies reported that miR-15a was also involved in hypoxia-induced gene expression regulation and cellular hypoxic adaptation. Yang et al found that hypoxia increases the level of miR-15a in rat cardiomyoblasts, and the inhibition of miR-15a significantly reduces cardiomyocyte apoptosis and the release of lactate dehydrogenase and malondialdehyde ( 33 ); Xue et al found that miR-15-16 transcription is repressed by hypoxia, which promotes tumor angiogenesis and hematogenous metastasis in tumor cells ( 34 ). We herein demonstrated that hypoxia enhances cell invasion and migration in the human osteosarcoma cell line MG63 through the downregulation of miR-15a and the upregulation of Bcl-2 ( Fig.…”