miRNA-27a Transcription Activated by c-Fos Regulates Myocardial Ischemia-Reperfusion Injury by Targeting ATAD3a

MicroRNA‐27a (miR‐27a) has been implicated in myocardial ischemia‐reperfusion injury (MIRI), but the underlying mechanism is not well understood. This study is aimed at determining the role of miR‐27a in MIRI and at investigating upstream molecules that regulate miR‐27a expression and its downstream target genes. miR‐27a expression was significantly upregulated in myocardia exposed to ischemia/reperfusion (I/R) and cardiomyocytes exposed to hypoxia/reoxygenation (H/R). c‐Fos could regulate miR‐27a expression by binding to its promoter region. Moreover, overexpression of miR‐27a led to a decrease in cell viability, an increase in LDH and CK‐MB secretion, and an increase in apoptosis rates. In contrast, suppression of miR‐27a expression resulted in the opposite effects. ATPase family AAA‐domain‐containing protein 3A (ATAD3a) was identified as a target of miR‐27a. miR‐27a regulated the translocation of apoptosis‐inducing factor (AIF) from the mitochondria to the nucleus and H/R‐induced apoptosis via the regulation of ATAD3a. It was found that inhibiting miR‐27a in vivo by injecting a miR‐27a sponge could ameliorate MIRI in an isolated rat heart model. In conclusion, our study demonstrated that c‐Fos functions as an upstream regulator of miR‐27a and that miR‐27a regulates the translocation of AIF from the mitochondria to the nucleus by targeting ATAD3a, thereby contributing to MIRI. These findings provide new insight into the role of the c‐Fos/miR‐27a/ATAD3a axis in MIRI.