Circ_0004214 prevents human cardiomyocytes from doxorubicin induced cardiotoxicity by governing the miR-22-3p/GATA4 pathway

Abstract

In a clinical setting, the likelihood of doxorubicin (DOX) causing cardiotoxicity is high. However, the underlying mechanism remains obscure. In this study, we investigated whether DOX toxicity is associated with the deregulation of circular RNA_0004212 (circ_0004214). Circ_0004214, microRNA-22-3p (miR-22-3p), and GATA binding protein 4 (GATA4) expression in human cardiomyocyte AC16 cells was detected via RT-qPCR. Lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and 4-hydroxynonenal (4-HNE) content were assessed using corresponding commercial kits. Cell viability and apoptosis were analyzed using cell counting kit-8 (CCK-8) and flow cytometry assays. Western blot assay was used to evaluate apoptosis-related markers and GATA4 protein levels. Dual-luciferase reporter validated the relationship between miR-22-3p and circ_0004214 or GATA4. Declined circ_0004214 was viewed in DOX-treated AC16 cells. DOX treatment weakened cell viability, and promoted oxidative stress and apoptosis, which was ameliorated via circ_0004214 overexpression. In addition, circ_0004214 promoted GATA4 expression by decoying miR-22-3p. Overall, the results have demonstrated that circ_0004214 protects against DOX-induced cardiotoxicity via governing miR-22-3p/GATA4 pathway, and thereby reveal promising therapeutic strategies against cardiotoxicity.