LAUSR

Abstract Purpose Cataract is the leading cause of visual impairment and reversible blindness. Despite advances in surgical removal of cataracts, cataract continues to be a leading public-health issue due to the complications after surgery. Circular RNAs (circRNAs) have been showed to be implicated in the pathophysiology of age-related cataract (ARC). Herein, this work elucidated the role and mechanism of circMED12L in the process of ARC. Methods Human lens epithelial cells (HLECs) were exposed to hydrogen peroxide (H2O2) in experimental groups. Levels of genes and proteins were measured by qRT-PCR and western blotting. Cell growth was evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The oxidative stress was assessed by detecting the activity of malondialdehyde, catalase, and superoxide dismutase. The interaction between miR-34a-5p and circMED12L or ALCAM (activated leukocyte cell adhesion molecule) was validated using dual-luciferase reporter and RNA immunoprecipitation assays. Results CircMED12L expression was lower in the lens epithelium of ARC patients and H2O2-induced HLECs compared with the normal individuals and untreated cells. Functionally, forced expression of circMED12L could alleviate H2O2-induced viability inhibition, as well as apoptotic and oxidative injury in HLECs. Mechanistically, circMED12L/miR-34a-5p/ALCAM constituted a feedback loop in HLECs. MiR-34a-5p was increased, while ALCAM was decreased in ARC patients and H2O2-induced HLECs. High expression of miR-34a-5p reversed the protective effects of circMED12L on HLECs under H2O2 treatment. Besides, inhibition of miR-34a-5p could repress H2O2-induced apoptotic and oxidative injury in HLECs, which were abolished by subsequent ALCAM knockdown. Conclusion Overexpression of circMED12L could protect against H2O2-induced apoptosis and oxidative stress in HLECs by miR-34a-5p/ALCAM axis.