TCF3 is epigenetically silenced by EZH2 and DNMT3B and functions as a tumor suppressor in endometrial cancer.

ABSTRACT: Endometrial cancer (EC) is the most common gynecological malignancy worldwide. However, the molecular mechanisms underlying EC progression are still largely unknown, and chemotherapeutic options for EC patients are currently very limited. In this study, we found that histone methyltransferase EZH2 and DNA methyltransferase DNMT3B were upregulated in EC samples from patients, and promoted EC cell proliferation as evidenced by assays of cell viability, cell cycle, colony formation. Mechanistically, we found that EZH2 promoted EC cell proliferation by epigenetically repressing TCF3, a direct transcriptional activator of CCKN1A (p21^WAF1/Cip1), in vitro and in vivo. In addition, we found that DNMT3B specifically methylated the TCF3 promoter, repressing TCF3 expression and acceleratin

SUBMITTER: Gui T 

PROVIDER: S-EPMC8630057 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature