STAT5 and TET2 Cooperate to Regulate FOXP3-TSDR Demethylation in CD4+ T Cells of Patients with Colorectal Cancer

The tumor-infiltrating Tregs are linked to colorectal cancer progression and outcome. FOXP3 is regarded as a critical developmental and functional factor for Tregs. FOXP3-TSDR demethylation is required for stable expression of FOXP3 and maintenance of Treg function. In our study, we found specific D...

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Bibliographic Details
Main Authors: Hulin Ma, Weishi Gao, Xiaoxia Sun, Weixing Wang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/6985031
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Summary:The tumor-infiltrating Tregs are linked to colorectal cancer progression and outcome. FOXP3 is regarded as a critical developmental and functional factor for Tregs. FOXP3-TSDR demethylation is required for stable expression of FOXP3 and maintenance of Treg function. In our study, we found specific DNA hypomethylation of FOXP3-TSDR in CD4+ T cells from colon tumor tissues as compared with normal colonic tissues. Moreover, we also found that the expression of STAT5 and TET2 was increased in CD4+ T cells from colon tumor tissues, and the superfluous STAT5 and TET2 binding to FOXP3-TSDR resulted in DNA hypomethylation. In conclusion, we have demonstrated that excessive amounts of STAT5 may bind more TET2 to the FOXP3-TSDR and upregulate FOXP3 expression via DNA demethylation. Our study improved the mechanism of FOXP3-TSDR hypomethylation in tumor-infiltrating CD4+ T cells of CRC patients.
ISSN:2314-8861
2314-7156