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This study investigates the functions of two key m<jats:sup>6<\/jats:sup>A regulators\u2014\u03b1\u2010ketoglutarate\u2010dependent dioxygenase alkB homolog 5 (ALKBH5) and KIAA1429\u2014in modulating BCa cell behavior. Expression levels of ALKBH5, KIAA1429, and Sonic Hedgehog (SHH) were examined in BCa tissues and adjacent normal tissues. Functional assays, including methylated RNA immunoprecipitation\u2010quantitative PCR (MeRIP\u2010qPCR), RNA immunoprecipitation (RIP), and RNA stability assessments, were performed in J82 BCa cells to explore the underlying mechanisms. Results revealed that KIAA1429 was significantly upregulated in BCa and promoted cell proliferation, migration, and invasion by enhancing m<jats:sup>6<\/jats:sup>A modification and stabilizing SHH mRNA, leading to activation of the Hedgehog signaling pathway. In contrast, ALKBH5, which was downregulated in BCa, acted as an m<jats:sup>6<\/jats:sup>A demethylase that destabilized SHH mRNA and attenuated Hedgehog pathway activity, thereby counteracting the oncogenic effects of KIAA1429. Moreover, overexpression of SHH reversed the inhibitory effects induced by KIAA1429 knockdown, confirming its role as a downstream effector. In conclusion, ALKBH5 and KIAA1429 exert opposing regulatory effects on BCa progression via m<jats:sup>6<\/jats:sup>A\u2010mediated modulation of SHH expression and Hedgehog signaling. These findings highlight SHH mRNA methylation as a central mechanism in BCa malignancy and identify ALKBH5 and KIAA1429 as potential therapeutic targets.<\/jats:p>","DOI":"10.1002\/mc.70004","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T08:59:40Z","timestamp":1750928380000},"page":"1473-1486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["KIAA1429 and AlkB Homolog 5 Regulate Bladder Cancer Progression via <i>N<\/i><sup>6<\/sup>\u2010Methyladenosine\u2010Dependent Modulation of Sonic Hedgehog Signaling"],"prefix":"10.1002","volume":"64","author":[{"given":"Zhimin","family":"Jiao","sequence":"first","affiliation":[{"name":"Department of Urology Wujin Hospital Affiliated With Jiangsu University Changzhou Jiangsu China"},{"name":"Department of Urology The Wujin Clinical College of Xuzhou Medical University Changzhou Jiangsu 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