Circ_0122396 Protects Human Lens Epithelial Cells from Hydrogen Peroxide-induced Injury by Binding to miR-15a-5p to Stimulate FGF1 Expression

Abstract

ABSTRACT Background Circular_0122396 (circ_0122396) has been reported to be downregulated in age-related cataract (ARC); however, the underlying mechanism remains unknown. The study aimed to reveal the role of circ_0122396 in ARC progression and underneath mechanism. Methods Hydrogen peroxide (H2O2) was employed to induce lens epithelial cells (SRA01/04) injury. The RNA expression of circ_0122396, microRNA-15a-5p (miR-15a-5p) and fibroblast growth factor 1 (FGF1) was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blot. Cell viability, proliferation and apoptosis were investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-Ethynyl-29-deoxyuridine and flow cytometry analysis, respectively. Oxidative stress was evaluated by superoxide dismutase and catalase activity assay kits and lipid peroxidation malondialdehyde assay kit. Online databases and mechanism assays were used to predict and identify the relationship between miR-15a-5p and circ_0122396 or FGF1. Results Circ_0122396 and FGF1 expression were significantly downregulated, but miR-15a-5p expression was upregulated in ARC tissues or/and H2O2-treated SRA01/04 cells in comparison with control groups. H2O2 treatment repressed cell proliferation and induced cell apoptosis and oxidative stress, which was attenuated after circ_0122396 overexpression. MiR-15a-5p, a target mRNA of circ_0122396, was found to participate in H2O2-triggered cell damage by interacting with circ_0122396. Additionally, FGF1 silencing attenuated miR-15a-5p inhibitors-mediated action. Importantly, circ_0122396 regulated FGF1 expression by interaction with miR-15a-5p in H2O2-treated SRA01/04 cells. Conclusion Circ_0122396 ameliorated H2O2-triggered cell injury by inducing FGF1 through sponging miR-15a-5p, providing a potential target for ARC therapy.