MicroRNA‐124 regulates lens epithelial cell apoptosis by affecting Fas alternative splicing by targeting polypyrimidine tract‐binding protein in age‐related cataract

Background Age‐related cataract (ARC) is a primary cause of visual blindness worldwide. Lens epithelial cell (LEC) apoptosis, in which Fas plays an essential role, is a vital cytological basis for cataractogenesis. However, the regulatory mechanism of Fas‐dependent LEC apoptosis is not well understood. This study aimed to investigate whether MicroRNA (miRNA)‐124 can regulate LEC apoptosis by targeting polypyrimidine tract‐binding protein (PTB) and thereby affecting Fas alternative splicing in ARC. Methods Lens capsule samples from patients with ARC and cornea donors with a transparent lens were collected. HLE‐B3 cells were cultured and treated with hydrogen peroxide (H2O2) to establish an apoptosis model in LECs. The expression of miRNA‐124, PTB, Fas, and Fas isoforms in tissues and cell lines was assessed by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR), western blotting, polyacrylamide gel electrophoresis, and flow cytometry. The miRNA‐124 mimic and inhibitor were transfected into HLE‐B3 cells, and the effects of the miRNA‐124/PTB/Fas pathway in LECs were assessed by analysis of their related targets. Results High expression of miRNA‐124 and membrane Fas (mFas) mRNA and decreased PTB expression were observed in the lens capsule samples. In cells undergoing H2O2‐induced apoptosis, mFas expression was increased, accompanied by decreased PTB and increased miRNA‐124 expression. Subsequently, miRNA‐124 upregulation suppressed PTB expression, elevated the mFas level without affecting total Fas expression and promoted apoptosis; miRNA‐124 downregulation exerted the opposite effects. Conclusion This study revealed that miRNA‐124 promotes LEC apoptosis in ARC by upregulating mFas through targeted inhibition of PTB. Moreover, the identification of the miRNA‐124/PTB/Fas pathway provides novel insight into Fas‐dependent LEC apoptosis.