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However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel m<jats:sup>7<\/jats:sup>G\u2010modified tsRNA, m<jats:sup>7<\/jats:sup>G\u20103\u2032\u2010tiRNA Lys<jats:sup>TTT<\/jats:sup> (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an m<jats:sup>7<\/jats:sup>G small RNA\u2010modified chip. Moreover, it is found that mtiRL, catalyzed by the tRNA m<jats:sup>7<\/jats:sup>G\u2010modifying enzyme mettl1, promotes bladder cancer (BC) malignancy in vitro and in vivo. Mechanistically, mtiRL is found to specifically bind the oncoprotein Annexin A2 (ANXA2) to promote its Tyr24 phosphorylation by enhancing the interactions between ANXA2 and Yes proto\u2010oncogene 1 (Yes1), leading to ANXA2 activation and increased p\u2010ANXA2\u2010Y24 nuclear localization in BC cells. Together, these findings define a critical role for mtiRL and suggest that targeting this novel m<jats:sup>7<\/jats:sup>G\u2010modified tsRNA can be an efficient way for to treat BC.<\/jats:p>","DOI":"10.1002\/advs.202400115","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T01:50:20Z","timestamp":1718761820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A Novel tsRNA, m<sup>7<\/sup>G\u20103\u2032 tiRNA Lys<sup>TTT<\/sup>, Promotes Bladder Cancer Malignancy Via Regulating ANXA2 Phosphorylation"],"prefix":"10.1002","volume":"11","author":[{"given":"Xiaoling","family":"Ying","sequence":"first","affiliation":[{"name":"Center for Translational Medicine The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou 510080 China"},{"name":"Department of Urology The Second Affiliated Hospital of Guangzhou Medical University  Guangzhou 510220 China"},{"name":"Guangdong 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