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Here we show that endothelin A receptor (ET<jats:sub>A<\/jats:sub>R) and ZEB1 expression is upregulated in mesenchymal ovarian cancer and correlates with poor prognosis. Notably, the expression of ET<jats:sub>A<\/jats:sub>R and ZEB1 negatively correlates with miR-200b\/c. These miRNAs, besides targeting ZEB1, impair ET<jats:sub>A<\/jats:sub>R expression through the 3\u2019UTR binding. ZEB1, in turn, restores ET<jats:sub>A<\/jats:sub>R levels by transcriptionally repressing miR-200b\/c. Activation of ET<jats:sub>A<\/jats:sub>R drives the expression of ZEB1 integrating the miR-200\/ZEB1 double negative feedback loop. The ET<jats:sub>A<\/jats:sub>R-miR-200b\/c-ZEB1 circuit promotes epithelial-mesenchymal transition, cell plasticity, invasiveness and metastasis. Of therapeutic interest, ET<jats:sub>A<\/jats:sub>R blockade with macitentan, a dual ET<jats:sub>A<\/jats:sub>R and ET<jats:sub>B<\/jats:sub>R antagonist, increases miR-200b\/c and reduces ZEB1 expression with the concomitant inhibition of metastatic dissemination. Collectively, these findings highlight the reciprocal network that integrates ET<jats:sub>A<\/jats:sub>R and ZEB1 axes with the miR-200b\/c regulatory circuit to favour metastatic progression in ovarian cancer.<\/jats:p>","DOI":"10.1038\/s42003-020-01404-3","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T11:02:55Z","timestamp":1605265375000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Targeting endothelin 1 receptor-miR-200b\/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-2777","authenticated-orcid":false,"given":"Rosanna","family":"Sestito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Cianfrocca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-013X","authenticated-orcid":false,"given":"Piera","family":"Tocci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rosan\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sacconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-2241","authenticated-orcid":false,"given":"Giovanni","family":"Blandino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-9522","authenticated-orcid":false,"given":"Anna","family":"Bagnato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"1404_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3322\/caac.21166","volume":"63","author":"R Siegel","year":"2013","unstructured":"Siegel, R., Naishadham, D. & Jemal, A. 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