biostudies-literatureLiu WNatural Science Foundation of Zhejiang ProvinceZhejiang Provincial Natural Science Foundation of ChinaHubei Chen Xiaoping Science and Technology Development FoundationGeneral Research Program of Zhejiang Provincial Department of HealthNational Natural Science Foundation of Chinae2407323https://www.ebi.ac.uk/biostudies/studies/S-EPMC11653675biostudies-literatureUnknown11(47)Ten-eleven translocation protein 1 (TET1) functions as an epigenetic regulatory molecule, mediating the majority of DNA demethylation, and plays a role in the development of different types of cancers by regulating the expression of proto-oncogenes and oncogenes. Here it is found that TET1 is highly expressed in cholangiocarcinoma (CCA) and is associated with a poor prognosis. In addition, TET1 promotes claudin-3 (CLDN3) transcription by targeting the CLDN3 promoter region between -16 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 epAdvanced science (Weinheim, Baden-Wurttemberg, Germany)PPM1G Inhibits Epithelial-Mesenchymal Transition in Cholangiocarcinoma by Catalyzing TET1 Dephosphorylation for Destabilization to Impair Its Targeted Demethylation of the CLDN3 Promoter.PMC116536758150210882173069LQ2023C0600032023KY12481974438CXPJJH12000001-2020228Kuai YWang QChen JWang BHuang WWang DQi YChen YWu GXiong FLiu WfalsePPM1G Inhibits Epithelial-Mesenchymal Transition in Cholangiocarcinoma by Catalyzing TET1 Dephosphorylation for Destabilization to Impair Its Targeted Demethylation of the CLDN3 Promoter.Ten-eleven translocation protein 1 (TET1) functions as an epigenetic regulatory molecule, mediating the majority of DNA demethylation, and plays a role in the development of different types of cancers by regulating the expression of proto-oncogenes and oncogenes. Here it is found that TET1 is highly expressed in cholangiocarcinoma (CCA) and is associated with a poor prognosis. In addition, TET1 promotes claudin-3 (CLDN3) transcription by targeting the CLDN3 promoter region between -16 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 ep2024-01-01T00:00:00Z2024 Dec2025-04-04T01:08:51.117Z2025-04-04T01:08:51.117ZS-EPMC116536753947780610.1002/advs.202407323