Knockdown of circRNA_0030042 Attenuates Heart Failure via miR-568/PRG4 Pathway.

Heart failure is a common heart disease and cause of death globally which is caused by structural and functional abnormalities. circRNA_0030042 is a newly discovered circRNA that derived from its host gene forkhead box O1 (FOXO1). However, the role of circRNA_0030042 in heart failure is not revealed. This study aims to explore the role of circRNA_0030042 in heart failure progression. In this study, AC16 cell heart failure model was induced in a medium containing 200 µM HO. circRNA_0030042 was markedly elevated in peripheral blood from patients with heart failure and HO-induced AC16 cells. Knockdown of hsa-circRNA_0030042 repressed the apoptosis of HO-induced AC16 cells and facilitated the viability of HO-induced AC16 cells. Besides, knockdown of hsa-circRNA_0030042 decreased iron ion level, ferroptotic markers ROS and MDA levels, increased GSH level, ferroptosis-associated proteins SLC7A11 and GPX4 protein expressions in HO-induced AC16 cells. In addition, hsa-circRNA_0030042 could interact with miR-568, and negatively modulate miR-568 expression in AC16 cells. miR-568 also targeted PRG4, and negatively modulated PRG4 expression. hsa-circRNA_0030042 positively regulated PRG4 via miR-568 in AC16 cells. Furthermore, knockdown of circRNA_0030042 promoted the proliferation, repressed the iron ion level, ROS level, increased SLC7A11 and GPX4 protein expressions in HO-induced AC16 cells via miR-568/PRG4 pathway. Finally, transverse aortic constriction (TAC) mice model were conducted by a thoracotomy procedure under the microscope. In vivo experiments showed that knockdown of mmu-circRNA_0030042 ameliorated cardiac dysfunction, decreased myocardial injury markers cTnI, CK-MB and BNP levels, relieved cardiac histopathological damage, decreased the apoptosis of heart tissue, and increased GSH, SLC7A11 and GPX4 protein expressions in heart tissue of TAC mice. Therefore, knockdown of circRNA_0030042 attenuated heart failure via miR-568/PRG4 pathway.