MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2

Xiangyi Kong; Xiaofeng Xu; Ling Zhou; Mengjing Zhu; Shuang Yao; Yue Ding; Tao Liu; Yijin Wang; Yan Zhang; Rong Li; Xiaoqiu Tang; Jingxian Ling; Jun Wu; Xianghong Zhu; Yuanyuan Gu; Huaijun Zhou

doi:10.1016/j.omtm.2020.09.013

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2

Mol Ther Methods Clin Dev. 2020 Sep 28:19:295-306. doi: 10.1016/j.omtm.2020.09.013. eCollection 2020 Dec 11.

Authors

Xiangyi Kong¹, Xiaofeng Xu¹, Ling Zhou², Mengjing Zhu², Shuang Yao², Yue Ding³, Tao Liu¹, Yijin Wang⁴, Yan Zhang¹, Rong Li¹, Xiaoqiu Tang¹, Jingxian Ling¹, Jun Wu¹, Xianghong Zhu¹, Yuanyuan Gu^{5

6}, Huaijun Zhou¹

Affiliations

¹ Department of Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
² Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.
³ Nanjing University Medical School, Nanjing 210008, China.
⁴ Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing 210008, China.
⁵ Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
⁶ Care Center, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China.

Abstract

Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.

Keywords: MTA1; ZEB2; endometriosis; epithelial-mesenchymal transition; resveratrol.