CircRbms1 fosters MST1 mRNA and protein levels to motivate myocardial ischaemia–reperfusion injury via autophagic status

Abstract

AbstractAimsAcute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia–reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury.Methods and resultsAn in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative real‐time PCR (qRT‐PCR) and western blot. Cellular proliferation, apoptosis, pyroptosis, and autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual‐luciferase reporter assay, RNA pull‐down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up‐regulated in A/R‐induced HCMs and acted as a sponge for miR‐142‐3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P < 0.05). CircRbms1 knockout reduced cell pyroptosis, improved autophagy and proliferation level in A/R‐induced HCMs (all P < 0.05). CircRbms1 knockout alleviated cardiac dysfunction and cell pyroptosis and enhanced autophagy and proliferation in mice through the miR‐142‐3p/MST1 axis.ConclusionsCircRbms1 inhibited the miR‐142‐3p/MST1 axis and played a protective role in myocardial I/R injury. It may provide a new therapeutic target for I/R heart injury.