Hsa_circ_0007059 promotes apoptosis and inflammation in cardiomyocytes during ischemia by targeting microRNA-378 and microRNA-383

Abstract

ABSTRACT Circular RNAs (circRNAs) are a class of non-coding RNA molecules that are associated with not only normal physiological functions but also various diseases, including cardiac diseases such as myocardial infarction (MI). The present study explored the potential role of circRNA_0007059 (circ_0007059) during MI pathogenesis using in vitro studies. Microarray and quantitative PCR analyses demonstrated elevated circ_0007059 expression and downregulated miR-378 and miR-383 expression in H2O2-treated mice cardiomyocytes and infarcted hearts of MI mouse model as compared those in relevant controls. Moreover, circ_0007059 knockdown improved cardiomyocyte viability after H2O2 treatment as revealed by the CCK-8 and colony formation assays. Flow cytometry and caspase activity assays demonstrated that circ_0007059 suppressed H2O2-induced cardiomyocyte apoptosis. Enzyme-linked immunosorbent assays and Western blotting revealed that inflammatory cytokine (interleukin-1β, interleukin-18 and C-C motif chemokine ligand 5) expression was induced by H2O2 treatment and that circ_0007059 repressed H2O2-induced inflammation. Bioinformatics analyses and dual-luciferase reporter assays showed that circ_0000759 acts as a miR-378 and miR-383 sponge. Furthermore, the upregulation or suppression of miR-378 and miR-383 expression in H2O2-treated cardiomyocytes had similar effects on the apoptosis and inflammation of cardiomyocytes as that of circ_0007059 knockdown or overexpression, respectively. Additionally, lentiviral shRNA-circ_0007059 administration to mice with MI considerably reduced the size of infarcted regions and promoted cardiac activity. Collectively, our findings suggest that circ_0007059 expression is upregulated in mice cardiomyocytes in response to oxidative stress and cardiac tissues of MI mouse model, suggesting its involvement in the pathogenesis of MI by targeting miR-378 and miR-383.