Ectopic circSTK39 Expression Ameliorates Hydrogen Peroxide-Induced Human Lens Epithelial Cell Apoptosis and Oxidative Stress through the miR-125a-5p/ERCC6 Pathway

Abstract

Purpose

More and more studies suggest that circular RNA (circRNA) is involved in the pathogenesis of age-related cataract (ARC). CircSTK39, a circular RNA, has inhibitory effects on cancer progression. However, there is no data regarding the role of circSTK39 in ARC occurrence and the underlying mechanism.

Methods

ARC cell model was established by inducing lens epithelial cells (SRA01/04) using hydrogen peroxide (H₂O₂). CircSTK39, microRNA-125a-5p (miR-125a-5p), and ERCC excision repair 6, chromatin remodeling factor (ERCC6) expression were detected by quantitative real-time polymerase chain reaction. Western blot was conducted to assess protein expression. Cell viability, proliferation, and apoptosis were investigated by cell counting kit-8 assay, 5-Ethynyl-29-deoxyuridine assay, and flow cytometry analysis, respectively. Oxidative stress was evaluated using commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were used to identify the relationship between miR-125a-5p and circSTK39 or ERCC6.

Results

CircSTK39 and ERCC6 expression were significantly downregulated, but miR-125a-5p expression was upregulated in the lens tissues of ARC patients and H₂O₂-treated SRA01/04 cells. H₂O₂ treatment led to decreased cell proliferation and increased cell apoptosis and oxidative stress, accompanied by the increases of C-caspase3 and Bax expression and the decrease of Bcl-2 expression; however, these effects were reversed after circSTK39 overexpression. MiR-125a-5p was found to participate in H₂O₂-triggered cell damage by interacting with circSTK39. Additionally, ERCC6 silencing inhibited circSTK39 overexpression-mediated action. Importantly, circSTK39 regulated ERCC6 expression by interaction with miR-125a-5p in H₂O₂-treated SRA01/04 cells.

Conclusion

The increased expression of circSTK39 ameliorated H₂O₂-induced SRA01/04 cell injury through the miR-125a-5p/ERCC6 pathway.

Keywords:

• Age-related cataract
• circSTK39
• miR-125a-5p
• ERCC6

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.