Abstract
Circular RNAs (circRNAs) are regulatory endogenous RNAs in human diseases by sponging microRNAs (miRNAs) to affect the gene expression. However, little research focused on the circRNA/miRNA/mRNA axis in diabetic cataract. This study was performed for the exploration of circRNA phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (circPAG1) in diabetic cataract. Human lens epithelial cells were treated with high glucose. The quantitative real-time polymerase chain reaction was used for the expression detection of circPAG1, microRNA-211-5p (miR-211-5p), and E2F transcription factor 3 (E2F3). Cell viability and proliferation were detected using Cell Counting Kit-8 assay and EdU assay. Cell apoptosis was analyzed by flow cytometry. The protein levels were measured by Western blot. Oxidative stress was assessed by malondialdehyde, reactive oxygen species, and superoxide dismutase via the corresponding detection kits. The target interaction was validated using the dual-luciferase reporter assay and RNA immunoprecipitation assay. The expression of circPAG1 was downregulated in diabetic cataract patients. The upregulation of circPAG1 could attenuate the high glucose-induced inhibition of cell viability and proliferation but promotion of cell apoptosis and oxidative stress. CircPAG1 served as a miR-211-5p sponge, and the protective role of circPAG1 was partly achieved by sponging miR-211-5p. MiR-211-5p targeted E2F3 and circPAG1 upregulated the E2F3 level by absorbing miR-211-5p. Inhibition of miR-211-5p repressed the high glucose-mediated cell dysfunction by increasing the expression of E2F3. This study clarified that circPAG1 protected human lens epithelial cells from the high glucose-induced cell damages by the mediation of miR-211-5p/E2F3 axis.