MiR-224-3p regulates ferroptosis and inflammation in lens epithelial cells by targeting ACSL4.

Abstract

In this study, we investigated the expression levels of miR-224-3p and inflammatory factors in the lens epithelium of patients with high myopia cataract (HMC) to determine how miR-224-3p/ACSL4 affects ferroptosis and inflammation in human lens epithelial cells (HLECs). The expression of miR-224-3p and ACSL4 in the capsules of patients was detected by qPCR, and RNA was extracted from each of the six capsules. To evaluate ferroptosis and inflammation, the level of expression of ACSL4, GPX4, and IL-6 was determined by immunohistochemistry, Transmission electron microscopy image showed the structure of mitochondria. The results of the PCR assays showed that the expression levels of miR-224-3p and IL-6 in the lens epithelium of HMC patients were significantly greater than those in ARC. ACSL4 and GPX4 in HMC were considerably lower than those in ARC. Electron microscopy images revealed that the mitochondria of HMC were significantly shrunken compared to those of ARC. A dual-luciferase report found miR-224-3p regulates ACSL4. PCR and WB assays revealed that ACSL4 was the downstream target gene of miR-224-3p. We also found that miR-224-3p promotes the proliferation and migration of HLECs. TNF-α (20 ng/mL) induced an inflammatory response in HLECs. Also, miR-224-3p effectively inhibited ferroptosis induced by erastin and decreased the level of expression of IL-6. Ferroptosis and inflammation occur in the eyes of HMC patients. Additionally, miR-224-3p increases the viability of HLECs by regulating ferroptosis and inflammation via ACSL4 targeting.