{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T05:03:10Z","timestamp":1785560590876,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies evidence that ubiquitin\u2010specific proteases (USPs) are associated with the occurrence and chemoresistance of T\u2010cell acute lymphoblastic leukemia (T\u2010ALL). <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) exerts a carcinogenic effect in human cancers and improves the mRNA stability of USPs. Whether ubiquitin\u2010specific protease 1 (USP1) controls chemoresistance of T\u2010ALL is unknown. Our study demonstrated that USP1 expression was upregulated in glucocorticoid (GC)\u2010resistant T\u2010ALL patients and cells (CEM\u2010C1). High expression of USP1 was correlated to the poor prognosis in T\u2010ALL patients. Silencing USP1 increased CEM\u2010C1 cell sensitivity to dexamethasone (Dex), reduced cell invasion, promoted cell apoptosis, and ameliorated glucocorticoid receptor (GR) expression. USP1 mediated T\u2010ALL chemoresistance by interacting with and deubiquitination of Aurora B. Overexpression of USP1 reversed the amelioration effect of Aurora B inhibitor on CEM\u2010C1 cell resistance to Dex. Mechanistically, ALKBH5 enhanced USP1 expression by reducing m6A level and mRNA stability in USP1 mRNA transcript. Downregulation of ALKBH5 reduced the levels of USP1 and Aurora B, facilitated CEM\u2010C1 cell sensitivity to Dex, apoptosis, and GR expression, suppressed cell invasion. However, overexpression of USP1 reversed all the effects of ALKBH5 on CEM\u2010C1 cells. In vivo results showed that tail vein injection of sh\u2010USP1 resulted in a significant prolongation of mouse survival, suppressed tumor growth, maintained the normal weight of mice, reduced USP1 expression and facilitated GR expression. In conclusion, inhibition of ALKBH5\u2010mediated m6A modification decreased USP1 expression and downregulation of USP1 ameliorated GC resistance of T\u2010ALL through suppressing Aurora B expression and elevating GR level.<\/jats:p>","DOI":"10.1002\/mc.23330","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T07:10:28Z","timestamp":1624605028000},"page":"644-657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["ALKBH5\u2010mediated m6A\u2010demethylation of USP1 regulated T\u2010cell acute lymphoblastic leukemia cell glucocorticoid resistance by Aurora B"],"prefix":"10.1002","volume":"60","author":[{"given":"Hongtao","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Hematology The Second Affiliated Hospital of Zhengzhou University Zhengzhou Henan 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