biostudies-literatureLiu JFundamental Research Funds for the Central UniversitiesResearch Fund of Zhongnan Hospital of Wuhan UniversityNational Natural Science Foundation of Chinae2403995https://www.ebi.ac.uk/biostudies/studies/S-EPMC11615784biostudies-literatureUnknown11(45)Bladder cancer (BLCA) is a prevalent cancer with high case-fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non-apoptotic form of cell death, is initiated by the lethal accumulation of iron-dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re-analysis of single-cell RNA data reveals a decrease in high-ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT pAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Deubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.PMC11615784YYXKNLJS202400182472733PTPP2024001RLYC20240010012042022dx0003SWYBK01-03Liu JJin WXiao YWang GYu JZhang RLi MJu LJiang WZhang YLuo YWei HZhou FWang XChen SWang YQian KfalseDeubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.Bladder cancer (BLCA) is a prevalent cancer with high case-fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non-apoptotic form of cell death, is initiated by the lethal accumulation of iron-dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re-analysis of single-cell RNA data reveals a decrease in high-ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT p2024-01-01T00:00:00Z2024 Dec2026-06-02T09:12:17.875Z2025-04-06T17:33:34.808ZS-EPMC116157843939237310.1002/advs.202403995