{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:48:20Z","timestamp":1791236900926,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lysine acetyltransferase 2A (KAT2A) is a transcriptional coactivator and a member of the Histone Acetyltransferase (HAT) family. While altered KAT2A activity has been implicated in various cancers, its role in bladder cancer (BLCA) remains poorly understood. Post\u2010translational modifications (PTMs), such as O\u2010GlcNAcylation, play a critical role in cancer biology. In this study, we investigated the impact of O\u2010GlcNAcylation on KAT2A stability and its oncogenic potential in BLCA. We analyzed 96 paired BLCA and normal tissue samples using quantitative real\u2010time PCR (qPCR) and immunohistochemistry to assess KAT2A expression. Functional assays, including siRNA\u2010mediated knockdown, co\u2010immunoprecipitation (co\u2010IP), ubiquitination, and chromatin immunoprecipitation (ChIP), were conducted in BLCA cell lines and xenograft models to understand KAT2A O\u2010GlcNAcylation mechanisms. We found that KAT2A expression was significantly increased in BLCA tissues. O\u2010GlcNAcylation at serine 583 (S583) stabilized KAT2A by inhibiting TRIM22\u2010mediated ubiquitination. Hyper\u2010O\u2010GlcNAcylation increased H3K9 acetylation and upregulated oncogenes like TGFB1, E2F1, and GPX4, promoting cell proliferation and tumor growth. Mutation of S583 destabilized KAT2A, impaired H3K9 acetylation, and suppressed oncogene expression. Our results highlight the pivotal role of KAT2A in BLCA and demonstrate that O\u2010GlcNAcylation at S583 is a crucial regulatory mechanism driving tumor progression. Targeting KAT2A O\u2010GlcNAcylation may provide a promising therapeutic strategy for BLCA patients.<\/jats:p>","DOI":"10.1111\/cas.70416","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:46:36Z","timestamp":1778546796000},"page":"2166-2180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["O\u2010\n                    <scp>GlcNAcylation<\/scp>\n                    of\n                    <scp>KAT2A<\/scp>\n                    Enhances Bladder Cancer Proliferation by Inhibiting the\n                    <scp>KAT2A<\/scp>\n                    \u2010\n                    <scp>TRIM22<\/scp>\n                    Interaction"],"prefix":"10.1111","volume":"117","author":[{"given":"Wenjie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Urology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 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Urology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqiang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Urology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5800-7573","authenticated-orcid":false,"given":"Jie","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Urology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Urology Peking Union Medical College Hospital, Chinese Academy of Medical 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