MiRNA-26a inhibits myocardial infarction-induced apoptosis by targeting PTEN via JAK/STAT pathways.

Abstract

Acute myocardial infarction (MI) is a common cause of the morbidity and mortality of cardiovascular diseases in the world. Acute MI lead to cardiovascular output after formation of myocardial ischemia and circulatory arrest in coronary heart diseases. However, the mechanisms underlying MI injury are poorly understood. We explored the part played by miR-26a in myocardial infarction (MI). Decreased miR-26a expression in H2O2-treated newborn murine ventricular cardiomyocytes (NMVCs) was observed, as well as in the infarcted heart of MI mouse model, compared to untreated NMVCs and healthy mouse heart tissue, respectively. Conversely, the upregulation of phosphatase and tensin homolog (PTEN) was observed in H2O2-treated NMVCs, and in infarcted hearts. An MTT assay and BrdU staining showed that H2O2 treatment attenuated cell viability in NMVCs, whereas miR-26a overexpression increased cell viability. Both TUNEL assay and flow cytometry (FC) displayed that miR-26a expression suppressed H2O2-induced cell apoptosis. Besides, miR-26a overexpression suppressed the upregulation of PTEN expression in H2O2-treated NMVCs by directly binding to PTEN 3'-UTR. PI3K/Akt and JAK/STAT signal transduction pathways were found to be regulated through cross-talk between miR-26a and PTEN. Furthermore, agomiR-26a treatment in MI mouse model considerably suppressed the size of the infarcted regions, and improved cardiac activity. MiR-26a expression in MI cardiac tissues was downregulated in response to H2O2 stress, whereas it could still protect against cell death by modulation of the PI3K/Akt and JAK/STAT signal transduction pathways by directly targeting PTEN.