Downregulation of circular RNA 00091761 protects against heart failure after myocardial infarction via microRNA-335-3p/ ASCL4 axis.

Abstract

Our research tended to explore the biological roles and expression status of circ_00091761 in HF after MI. The hypoxia reoxygenation (H/R) injured H9c2 cells model was constructed to simulate HF after MI. The expression of circ_0091761 was examined in H/R injured H9c2 cells by qRT-PCR. Then, the effect of circ_0091761 expression on the proliferation of H/R injured H9c2 cells was evaluated by CCK-8 along with TUNEL assay. Secretion of lactate dehydrogenase (LDH), reactive oxygen species (ROS), Fe2+, glutathione (GSH), and malondialdehyde (MDA) was measured to evaluate cell ferroptosis of H/R injured H9c2 cells, along with protein levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor protein (TFRC). Luciferase reporter as well as RNA pull-down assays revealed the binding relationship between miR-335-3p and circ_0091761 or ASCL4. Circ_0091761 was upregulated in H/R injured H9c2 cells. Knockdown of circ_0091761 promoted cell proliferation and suppressed ferroptosis of H/R injured H9c2 cells. Interestingly, circ_0091761 sponges miR-335-3p to upregulate acyl-CoA synthetase long-chain family member 4 (ACSL4) expression. miR-335-3p inhibitor attenuated the effects of circ_0091761 knockdown on cell proliferation and ferroptosis in H/R injured H9c2 cells. Additionally, upregulated ACSL4 abrogated elevated miR-335-3p-induced effects on H/R injured H9c2 cells. Circ_0091761 inhibited cell proliferation and accelerated ferroptosis of H/R injured H9c2 cells by sponging miR-335-3p to upregulated TFRC axis. Therefore, Inhibition of circ_0091761 may protect against HF after MI.