m6A demethylase FTO regulates the apoptosis and inflammation of cardiomyocytes via YAP1 in ischemia-reperfusion injury.

ABSTRACT

Reperfusion therapy after acute myocardial infarction can induce myocardial ischemia-reperfusion injury (IRI). Novel evidence has illustrated that N6-methyladenosine (m6A) modification modulates the myocardial IRI progression. Here, our study focuses on the role of m6A methyltransferase fat mass and obesity-associated protein (FTO) in myocardial ischemia/reoxygenation injury and explores potential regulatory mechanisms. Results discovered that FTO down-expressed in myocardial IRI mice and hypoxia/reoxygenation (H/R)-induced cardiomyocytes. Functionally, FTO overexpression attenuated the H/R-induced apoptosis and inflammation of cardiomyocytes. Mechanistically, methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP-qPCR) assay and RIP assay revealed that Yap1 mRNA acted as the target of FTO in cardiomyocytes. Moreover, FTO uninstalled the methylation of Yap1 mRNA, and enforced the stability of Yap1 mRNA. Taken together, our study reveals the role of FTO in H/R-induced myocardial cell injury via m6A-dependent manner, which may provide a new approach to improve myocardial IRI.