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

INTRODUCTION

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).

MATERIAL AND METHODS

Decreased miR-26a expression in HO-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 HO-treated NMVCs, and in infarcted hearts. An MTT assay and BrdU staining showed that HO 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 HO-induced cell apoptosis. Besides, miR-26a overexpression suppressed the upregulation of PTEN expression in HO-treated NMVCs by directly binding to PTEN 3'-UTR.

RESULTS

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.

CONCLUSIONS

MiR-26a expression in MI cardiac tissues was downregulated in response to HO 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.