No abstract

Background: Myocardial cell injury is a key event in acute myocardial infarction (AMI). The involvement of circular RNA (circRNA) in cardiovascular disease has aroused much attention. The purpose of this study was to uncover the role of circRNA coactivator-associated arginine methyltransferase 1 (circCARM1) in cell model of AMI.Methods: Myocardial cells (AC16) were subjected to oxygen glucose deprivation/reoxygenation (OGD/R) to induce AMI models. Expression analysis of circCARM1, miR-338-3p and tumor necrosis factor receptor-associated factor 3 (TRAF3) was conducted using Real-time quantitative PCR (RT-qPCR). Cell viability, proliferation and apoptosis were assessed by CCK-8, EdU or flow cytometry assay. Oxidative stress was evaluated according to MDA level and SOD activity using commercial kits and the protein levels of NOX2 and SOD2 using western blot. The release of inflammatory factors was measured using ELISA kits. The predicted binding association between miR-338-3p and circCARM1 or TRAF3 was validated by pull-down assay or dual-luciferase reporter assay.Results: CircCARM1 was overexpressed in OGD/R-treated AC16 cells. OGD/R suppressed AC16 cell viability and proliferation and promoted apoptosis, oxidative stress and inflammation, while circCARM1 knockdown alleviated these injuries. MiR-338-3p was targeted by circCARM1, and miR-338-3p repression reversed the effects of circCARM1 knockdown. In addition, TRAF3 was a downstream target of the circCARM1/miR-338-3p axis, and TRAF3 reintroduction reversed the effects of miR-338-3p overexpression, thus recovering OGD/R-induced AC16 cell injuries. TRAF3 knockdown attenuated the activity of IkBα/P65 signaling pathway via modulating the miR-338-3p/TRAF3 axis in OGD/R-treated AC16 cells.Conclusion: CircCARM1 governed the miR-338-3p/TRAF3 axis to activate the IkBα/P65 signaling pathway, thus contributing to OGD/R-induced AC16 cell injuries.