{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:11:27Z","timestamp":1767863487252,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672560"],"award-info":[{"award-number":["81672560"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772773"],"award-info":[{"award-number":["81772773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Ovarian cancer is one of the most frequent carcinomas in females, and the occurrence rate is still rising despite many advances made. The pathogenesis of ovarian cancer remains greatly unclear. Here, we investigated the mechanisms of ovarian cancer, with the focus on circATRNL1. Human ovarian cancer tissues and cell lines were used to examine levels of circATRNL1, miR\u2010378, Smad4, AKT, and other proliferation\u2010related and migration\u2010related proteins. Cellular assays were used to determine cancer cell proliferation, invasion, migration, apoptosis, and angiogenesis. We validated the interactions of circATRNL1\/miR\u2010378 and miR\u2010378\/Smad4, and a mouse tumor xenograft model was employed to assess the effect of circATRNL1 on tumor growth and metastasis <jats:italic>in\u00a0vivo<\/jats:italic>. We found that circATRNL1 was decreased while miR\u2010378 was increased in human ovarian cancer tissues and cells. circATRNL1 bound to miR\u2010378 while miR\u2010378 directly targeted Smad4. Overexpression of circATRNL1 or knockdown of miR\u2010378 suppressed angiogenesis and ovarian cancer cell proliferation, invasion, and migration via decreasing proliferation\u2010 and migration\u2010related proteins via miR\u2010378 or Smad4, respectively. Overexpression of circATRNL1 restrained ovarian cancer growth and abdominal metastasis <jats:italic>in\u00a0vivo<\/jats:italic>. Our findings indicate that circATRNL1 acts as a miR\u2010378 sponge to active Smad4 signaling and suppresses angiogenesis and ovarian cancer metastasis.<\/jats:p>","DOI":"10.1002\/1878-0261.12893","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T08:05:26Z","timestamp":1609229126000},"page":"1217-1233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["CircATRNL1 activates Smad4 signaling to inhibit angiogenesis and ovarian cancer metastasis via miR\u2010378"],"prefix":"10.1002","volume":"15","author":[{"given":"Juan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics the First Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics the First People's Hospital of Yancheng China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Hua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics the First Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang\u2010Rong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics the First Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics the First Affiliated Hospital of Soochow University Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6009-4369","authenticated-orcid":false,"given":"You\u2010Guo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology 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