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FOXO3, a key regulator of aging, apoptosis, and oxidative stress\u2010induced cell death, was investigated for its role and regulatory mechanisms in UVB\u2010induced oxidative stress using human lens epithelial cells (HLECs). A progressive decrease in FOXO3 protein expression was observed in the lens capsules across various stages of cataract progression, as well as in UVB\u2010exposed animal models and UVB\u2010treated HLECs. Functional assays demonstrated that FOXO3 overexpression protected HLECs against UVB\u2010induced damage by increasing cell viability, reducing reactive oxygen species (ROS) generation, and suppressing apoptosis. Furthermore, we demonstrated that the AMPK\/FOXO3 signaling pathway is involved in this protective mechanism, as AMPK inhibition restored FOXO3 expression and mitigated UVB\u2010induced cellular damage. Additionally, lncRNA SNHG12 was identified as a potential candidate regulated by FOXO3. Overexpressing FOXO3 in HLECs resulted in reduced lncRNA SNHG12 expression, whereas FOXO3 knockdown elevated lncRNA SNHG12 levels. Further luciferase reporter assays validated their interaction, revealing FOXO3 as a negative regulator of SNHG12 expression. Moreover, the knockdown of SNHG12 significantly attenuated apoptosis and oxidative stress induced by UVB in HLECs. In conclusion, these findings suggest that FOXO3 alleviates UVB\u2010induced oxidative stress in lens epithelial cells through the AMPK\/FOXO3 pathway and regulation of SNHG12, providing a potential therapeutic target for ARC.<\/jats:p>","DOI":"10.1096\/fj.202501265rr","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T14:33:13Z","timestamp":1757428393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>FOXO3<\/scp>\n                    Protects Lens Epithelial Cells From\n                    <scp>UVB<\/scp>\n                    \u2010Induced Oxidative Stress via the\n                    <scp>AMPK<\/scp>\n                    \/\n                    <scp>FOXO3<\/scp>\n                    Signaling Pathway"],"prefix":"10.1096","volume":"39","author":[{"given":"Yang","family":"Sun","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye 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