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Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis |
| Authors: | Zhang, Qi Browse this author | | Dong, Peixin Browse this author →KAKEN DB | | Liu, Xishi Browse this author | | Sakuragi, Noriaki Browse this author →KAKEN DB | | Guo, Sun-Wei Browse this author |
| Issue Date: | 28-Jul-2017 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Scientific Reports |
| Volume: | 7 |
| Start Page: | 6804 |
| Publisher DOI: | 10.1038/s41598-017-06920-7 |
| 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/66971 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 董 培新
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