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However, their function in ESCC remains unknown. This study investigates AR\u2010regulated snoRNAs and their mechanistic contributions to ESCC pathogenesis. SNORA80B is identified as the most AR\u2010responsive snoRNA with oncogenic activity by transcriptomic profiling. Beyond its classical role, SNORA80B stabilizes cholesterol metabolism transcripts via N\u2076\u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A)\u2010YTHDC1, driving cholesterol\/DHT accumulation and lipid droplets (LDs) formation. A feedforward loop is observed wherein DHT\u2010activated AR upregulates SNORA80B, which further enhances AR signaling through cholesterol metabolic reprogramming. Clinofibrate, identified as a SNORA80B inhibitor through high\u2010throughput screening of FDA\u2010approved drugs, disrupts this axis and demonstrates synergistic effects with cisplatin, overcoming resistance in ESCC. The study reveals a novel non\u2010classical function of SNORA80B in ESCC, establishing it as a key effector of AR\u2010driven metabolic reprogramming through m\u2076A\u2010dependent regulation. The repurposing of clinofibrate demonstrates the therapeutic potential of targeting snoRNA\u2010mediated pathways, providing both mechanistic insights and a clinically translatable strategy for ESCC treatment. These findings redefine the functional scope of snoRNAs in cancer pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509574","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T10:01:58Z","timestamp":1762164118000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinofibrate Disrupts the SNORA80B\/YTHDC1\u2010Driven M6A Modification to Suppress Cholesterol Metabolism and Cisplatin Resistance in ESCC"],"prefix":"10.1002","volume":"13","author":[{"given":"Hongyu","family":"Yuan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100021 P. R. 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