Abstract
MicroRNAs (miRNAs) are critical regulatory factors in myocardial ischemia/reperfusion (I/R) injury. The miRNA miR-30c-5p has been reported as a key mediator in several myocardial abnormalities. However, the precise roles and mechanisms of miR-30c-5p in myocardial I/R injury remain not well-studied. This project aimed to explore the potential function of this miRNA in mediating myocardial I/R injury. Significant induction of miR-30c-5p was observed in myocardial tissue of rats with myocardial I/R injury in vivo and cardiomyocytes with hypoxia/re‑oxygenation (H/R) injury in vitro. Functional studies elucidated that forced expression of miR-30c-5p in rats effectively reduced infarct area, cardiac apoptosis, oxidative stress and inflammation induced by myocardial I/R injury. Moreover, in vitro cardiomyocytes with forced expression of miR-30c-5p were also protected from H/R-induced apoptosis, oxidative stress and inflammation. Importantly, BTB domain and CNC homology 1 (Bach1) was identified as a new target of miR-30c-5p. miR-30c-5p was shown to promote the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via the inhibition of Bach1. The re-expression of Bach1 reversed miR-30c-5p-mediated-cardioprotective effects against myocardial I/R injury in vivo or H/R injury in vitro. Overall, our results demonstrate that forced expression of miR-30c-5p exhibited beneficial effects against myocardial I/R injury through enhancement of Nrf2 activation via inhibition of Bach1. This work reveals a novel molecular mechanism for myocardial I/R injury at the miRNA level and suggests a therapeutic value of miR-30c-5p in treatment of myocardial I/R injury.