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 (H2 O2 ) 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 H2 O2 -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.Keywords: Fas; PTB; RNA alternative splicing; age-related cataract; microRNA-124.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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