CircMED12L Protects Against Hydrogen Peroxide-induced Apoptotic and Oxidative Injury in Human Lens Epithelial Cells by miR-34a-5p/ALCAM axis.

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 (HO) 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 HO-induced HLECs compared with the normal individuals and untreated cells. Functionally, forced expression of circMED12L could alleviate HO-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 HO-induced HLECs. High expression of miR-34a-5p reversed the protective effects of circMED12L on HLECs under HO treatment. Besides, inhibition of miR-34a-5p could repress HO-induced apoptotic and oxidative injury in HLECs, which were abolished by subsequent ALCAM knockdown.

Conclusion: Overexpression of circMED12L could protect against HO-induced apoptosis and oxidative stress in HLECs by miR-34a-5p/ALCAM axis.