Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis

Abstract EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with...

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Autores principales:	Qi Zhang, Peixin Dong, Xishi Liu, Noriaki Sakuragi, Sun-Wei Guo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f15d45224d744c4a05d733265b7d54b
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spelling	oai:doaj.org-article:5f15d45224d744c4a05d733265b7d54b2021-12-02T16:06:50ZEnhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis10.1038/s41598-017-06920-72045-2322https://doaj.org/article/5f15d45224d744c4a05d733265b7d54b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06920-7https://doaj.org/toc/2045-2322Abstract EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity. Conversely, overexpression of EZH2 induced the expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor, significantly inhibited the growth of endometriotic lesions and improved generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27 and H3K9 trimethylation levels in endometriotic epithelial cells. These data identify EZH2 as a novel driver of EMT in endometriosis, implicates the link between wound healing and epigenetic changes in the context of endometriosis, and underscore the role of platelets in the development of endometriosis.Qi ZhangPeixin DongXishi LiuNoriaki SakuragiSun-Wei GuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qi Zhang Peixin Dong Xishi Liu Noriaki Sakuragi Sun-Wei Guo Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
description	Abstract EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity. Conversely, overexpression of EZH2 induced the expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor, significantly inhibited the growth of endometriotic lesions and improved generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27 and H3K9 trimethylation levels in endometriotic epithelial cells. These data identify EZH2 as a novel driver of EMT in endometriosis, implicates the link between wound healing and epigenetic changes in the context of endometriosis, and underscore the role of platelets in the development of endometriosis.
format	article
author	Qi Zhang Peixin Dong Xishi Liu Noriaki Sakuragi Sun-Wei Guo
author_facet	Qi Zhang Peixin Dong Xishi Liu Noriaki Sakuragi Sun-Wei Guo
author_sort	Qi Zhang
title	Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
title_short	Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
title_full	Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
title_fullStr	Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
title_full_unstemmed	Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
title_sort	enhancer of zeste homolog 2 (ezh2) induces epithelial-mesenchymal transition in endometriosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5f15d45224d744c4a05d733265b7d54b
work_keys_str_mv	AT qizhang enhancerofzestehomolog2ezh2inducesepithelialmesenchymaltransitioninendometriosis AT peixindong enhancerofzestehomolog2ezh2inducesepithelialmesenchymaltransitioninendometriosis AT xishiliu enhancerofzestehomolog2ezh2inducesepithelialmesenchymaltransitioninendometriosis AT noriakisakuragi enhancerofzestehomolog2ezh2inducesepithelialmesenchymaltransitioninendometriosis AT sunweiguo enhancerofzestehomolog2ezh2inducesepithelialmesenchymaltransitioninendometriosis
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Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis

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