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Here it is found that TET1 is highly expressed in cholangiocarcinoma (CCA) and is associated with a poor prognosis. In addition, TET1 promotes claudin\u20103 (CLDN3) transcription by targeting the CLDN3 promoter region between \u221216 and 512 for demethylation. PPM1G functions as a protein dephosphorylase, catalyzing the dephosphorylation of TET1. This results in the destabilization of the TET1 protein, thereby impairing the targeting of the CLDN3 promoter for demethylation. Two phosphatase inhibitors, staurosporine and AZD0156, inhibit epithelial\u2010to\u2010mesenchymal transition (EMT) in cholangiocarcinoma cells by suppressing TET1 expression. In conclusion, it is also demonstrated that PPM1G can be employed as a therapeutic target to impede the progression of CCA by catalyzing the dephosphorylation of TET1, which diminishes the capacity of TET1 to target the CLDN3 promoter to activate transcription and inhibit EMT in CCA.<\/jats:p>","DOI":"10.1002\/advs.202407323","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T23:23:41Z","timestamp":1730330621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PPM1G Inhibits Epithelial\u2013Mesenchymal Transition in Cholangiocarcinoma by Catalyzing TET1 Dephosphorylation for Destabilization to Impair Its Targeted Demethylation of the CLDN3 Promoter"],"prefix":"10.1002","volume":"11","author":[{"given":"Wenzheng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biliary\u2010Pancreatic Surgery Tongji Hospital Tongji Medical College Huazhong University of 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