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To address these issues, we detected m6A levels in normal, eutopic, and ectopic endometrium and found the m6A levels decreased in eutopic and ectopic endometrium compared with normal endometrium. In addition, we proved that methyltransferase-like 3 (METTL3) downregulation accounted for m6A reduction in endometriosis. Furthermore, we observed that METTL3 knockdown facilitated the migration and invasion of human endometrial stromal cells (HESCs), whereas METTL3 overexpression exerted opposite effects, suggesting that METTL3 downregulation might contribute to endometriosis development by enhancing cellular migration and invasion. Mechanistically, METTL3-dependent m6A was involved in the DGCR8-mediated maturation of primary microRNA126 (miR126 and pri-miR126). Moreover, miR126 inhibitor significantly enhanced the migration and invasion of METTL3-overexpressing HESCs, whereas miR126 mimics attenuated the migration and invasion of METTL3-silenced HESCs. Our study revealed the METTL3\/m6A\/miR126 pathway, whose inhibition might contribute to endometriosis development by enhancing cellular migration and invasion. It also showed that METTL3 might be a novel diagnostic biomarker and therapeutic target for endometriosis.<\/jats:p>","DOI":"10.1093\/biolre\/ioab152","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T08:31:05Z","timestamp":1628757065000},"page":"1221-1233","source":"Crossref","is-referenced-by-count":65,"title":["Inhibition of METTL3\/m6A\/<i>miR126<\/i> promotes the migration and invasion of endometrial stromal cells in endometriosis"],"prefix":"10.1093","volume":"105","author":[{"given":"Xiaoou","family":"Li","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology , Union Hospital, Tongji Medical College, , Wuhan, Hubei, China"},{"name":"Huazhong University of Science and Technology , Union Hospital, Tongji Medical College, , Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology , Union Hospital, Tongji Medical College, , Wuhan, Hubei, China"},{"name":"Huazhong University of Science and Technology , Union Hospital, Tongji Medical College, , Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology , Union Hospital, Tongji Medical College, , Wuhan, Hubei, China"},{"name":"Huazhong University of Science and Technology , Union Hospital, Tongji Medical College, , Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology , , Detroit, MI, USA"},{"name":"Wayne State University , , Detroit, MI, 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