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miR-24-3p mediates Keap1/Nrf2 axis to promote autophagy and thereby inhibit lens epithelial cell early senescence

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机构: [1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, 1 Dongjiaominxiang, Beijing 100730, Peoples R China [2]Chongqing Med Univ, Clin Coll 5, 439 Xuanhua Rd, Chongqing 402160, Peoples R China [3]Fifth Peoples Hosp Hengshui, Dept Ophthalmol, 1638 West Shengli Rd, Hengshui 053000, Hebei, Peoples R China
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关键词: miR-24-3p Age-related cataract Keap1 Lens epithelial cells Senescence

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BackgroundmicroRNA-24-3p (miR-24-3p) has been identified as a diagnostic biomarker for age-related cataracts (ARC) and is implicated in the apoptosis of lens epithelial cells (LECs). However, its role in LECs senescence and the underlying regulatory mechanisms remain poorly understood. In this study, we investigated the functional involvement of miR-24-3p in ARC pathogenesis and elucidated its molecular mechanisms.MethodsThirty specimens of lens anterior capsule tissues were collected from patients diagnosed with ARC to assess miR-24-3p expression. Autophagic vesicles in LECs were visualized using monodansylcadaverine (MDC) staining, while cellular senescence was evaluated via senescence-associated beta-galactosidase (SA-beta-gal) staining.ResultsReverse transcription quantitative polymerase chain reaction (RT-qPCR) revealed significant downregulation of miR-24-3p in LECs of ARC patients, which exhibited an inverse correlation with senescence. The direct targeting interaction between miR-24-3p and the 3 '-UTR region of Keap1 mRNA was confirmed using a dual-luciferase reporter assay. Mechanistically, miR-24-3p was demonstrated to activate autophagic flux through modulation of the kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) signaling axis. Functional studies showed that miR-24-3p overexpression suppressed Keap1 protein levels while enhancing nuclear translocation of Nrf2. Notably, the anti-senescence effect of miR-24-3p was abolished following Nrf2 knockdown or pharmacological autophagy inhibition with 3-methyladenine (3-MA).ConclusionsA novel miR-24-3p/Keap1/Nrf2 signaling axis implicated in the senescence of LECs. miR-24-3p may be a promising therapeutic target for cataract intervention.

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出版当年[2025]版:
大类 | 4 区 医学
小类 | 4 区 眼科学
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大类 | 4 区 医学
小类 | 4 区 眼科学
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出版当年[2023]版:
Q3 OPHTHALMOLOGY
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Q3 OPHTHALMOLOGY

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第一作者机构: [1]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, 1 Dongjiaominxiang, Beijing 100730, Peoples R China
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