miR-379-3p activates the MAPK/JNK/p38 pathway by negatively targeting DUSP1 expression to promote myocardial ischemia-reperfusion injury.

Abstract

BackgroundMyocardial ischemia-reperfusion injury (MI/RI) is a primary cause of cardiomyocyte death in various cardiovascular diseases. MicroRNAs (miRNAs) play significant roles in MI/RI.ObjectiveThis study aims to elucidate the function and mechanism of miR-379-3p in this context.MethodsThe Cell Counting Kit 8 (CCK-8) and flow cytometry were utilized to assess the proliferation and apoptosis of cardiomyocytes. The expression levels of cardiomyocyte injury-related proteins, including LDHA, cTnT, CK-MB, and cTnI, were measured using enzyme-linked immunoassay (ELISA) kits. The targeted regulatory relationship between miR-379-3p and dual-specificity protein phosphatase 1 (DUSP1) was investigated through dual luciferase reporter gene assays. Additionally, the expression levels of miR-379-3p/DUSP1 and mitogen-activated protein kinases (MAPKs) signaling pathway in MI/RI were evaluated using Western blotting.ResultsThe expression of miR-379-3p was significantly elevated in MI/RI, and the inhibition of miR-379-3p notably alleviated MI/RI. The specific binding of miR-379-3p to the 3'UTR of DUSP1 mRNA was confirmed by dual luciferase reporter gene assays. Furthermore, miR-379-3p exacerbated cardiomyocyte injury by negatively regulating DUSP1. Ultimately, miR-379-3p activated the MAPK/JNK/p38 pathway by downregulating DUSP1 expression, thereby promoting MI/RI.ConclusionsmiR-379-3p activates the MAPK/JNK/p38 pathway through the negative regulation of DUSP1 expression to promote MI/RI.