Snail/PRMT5/NuRD Complex Contributes to DNA Hypermethylation in Cervical Cancer by TET1 Inhibition

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2021 May 6

PMID 33953349

Citations 29

Authors

Jie Gao

Ruiqiong Liu

Dandan Feng

Wei Huang

Miaomiao Huo

Jingyao Zhang

Shuai Leng

Yang Yang

Tianshu Yang

Xin Yin

Xu Teng

Hefen Yu

Baowen Yuan

Yan Wang

Affiliations

Soon will be listed here.

Abstract

The biological function of PRMT5 remains poorly understood in cervical cancer metastasis. Here, we report that PRMT5 physically associates with the transcription factor Snail and the NuRD(MTA1) complex to form a transcriptional-repressive complex that catalyzes the symmetrical histone dimethylation and deacetylation. This study shows that the Snail/PRMT5/NuRD(MTA1) complex targets genes, such as TET1 and E-cadherin, which are critical for epithelial-mesenchymal transition (EMT). This complex also affects the conversion of 5mC to 5hmC. This study demonstrates that the Snail/PRMT5/NuRD(MTA1) complex promotes the invasion and metastasis of cervical cancer in vitro and in vivo. This study also shows that PRMT5 expression is upregulated in cervical cancer and various human cancers, and the PRMT5 inhibitor EPZ015666 suppresses EMT and the invasion potential of cervical cancer cells by disinhibiting the expression of TET1 and increasing 5hmC, suggesting that PRMT5 is a potential target for cancer therapy.

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