Circular RNA circZNF292 regulates H2O2‐induced injury in human lens epithelial HLE‐B3 cells depending on the regulation of the miR‐222‐3p/E2F3 axis

Abstract

Circular RNAs (circRNAs) play important roles in the pathogenesis of age‐related cataract (ARC). CircRNA zinc finger protein 292 (circZNF292, hsa_circ_0004058) is downregulated in ARC lens capsules. Here, we focused on its precise roles in oxidative stress underlying the pathogenesis of ARC. CircZNF292, microRNA (miR)‐222‐3p, and E2F transcription factor 3 (E2F3) were quantified by quantitative real‐time polymerase chain reaction or western blot. Cell viability was assessed by the cell counting kit‐8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. The activities of superoxide dismutase, catalase, and malondialdehyde were measured using the corresponding assay kit. Targeted correlations among circZNF292, miR‐222‐3p, and E2F3 were verified by the dual‐luciferase reporter, RNA immunoprecipitation and RNA pull‐down assays. Our data showed that circZNF292 was downregulated in ARC tissues and H2O2‐treated human lens epithelial B3 (HLE‐B3) cells. Increased expression of circZNF292 alleviated H2O2‐induced cell viability suppression, apoptosis promotion, and oxidative stress enhancement. Mechanistically, circZNF292 directly targeted miR‐222‐3p, and circZNF292 regulated E2F3 expression through miR‐222‐3p. MiR‐222‐3p was a functional mediator of circZNF292 in modulating H2O2‐induced injury in HLE‐B3 cells. Furthermore, reduced level of miR‐222‐3p ameliorated H2O2‐induced HLE‐B3 cell damage by upregulating E2F3. Our present study demonstrated that increased expression of circZNF292 ameliorated H2O2‐induced injury in HLE‐B3 cells at least in part through the miR‐222‐3p/E2F3 axis, highlighting a novel insight into the involvement of circRNAs in the pathogenesis of ARC.