{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T23:19:00Z","timestamp":1771975140845,"version":"3.50.1"},"reference-count":48,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101771"],"award-info":[{"award-number":["82101771"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Spontaneous abortion (SA) is a common disorder in early pregnancy. Circular RNAs (circRNAs) have been reported to exert important regulatory effects on trophoblast function and embryo development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The aim of this study was to explore whether and how circRNAs regulate trophoblast function in SA during early pregnancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cell proliferation, 5-bromo-2-deoxyuridine (BrdU) staining, Transwell, immunofluorescence, Western blot, RNA pull-down, and dual luciferase reporter assays were performed to investigate the effect of circRNA cyclin B1 (circ-CCNB1) on trophoblast function in HTR-8\/SVneo and JEG-3 cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>An in vitro study demonstrated that upregulation of circ-CCNB1 significantly inhibited trophoblast proliferation and invasion compared with the controls using HTR-8\/SVneo and JEG-3 cells, respectively. Moreover, miR-223 was downregulated in the villous tissues of patients with SA and was further predicted and shown to negatively interact with circ-CCNB1, which is involved in trophoblast proliferation and invasion. Using bioinformatics tools and subsequent RNA pull-down and dual luciferase assays, we found that miR-223 directly targets seven in absentia homolog-1 (SIAH1) and that upregulation of miR-223 decreased circ-CCNB1-induced SIAH1 expression levels in HTR-8\/SVneo cells. Interestingly, upregulation of circ-CCNB1 suppressed trophoblast proliferation and invasion through inhibition of CCNB1 nuclear translocation induced by SIAH1. Downregulation of SIAH1 enhanced circ-CCNB1-suppressed CCNB1 nuclear protein expression in trophoblast cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Circ-CCNB1 served as a modulator of trophoblast proliferation and invasion by sponging miR-223, thus forming a regulatory network of circ-CCNB1\/miR-223\/SIAH1 in modulating CCNB1 nuclear translocation, which enabled us to elucidate the molecular mechanisms involved in normal embryo implantation or in SA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/endocr\/bqac093","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T17:35:48Z","timestamp":1655919348000},"source":"Crossref","is-referenced-by-count":13,"title":["Circ-CCNB1 Modulates Trophoblast Proliferation and Invasion in Spontaneous Abortion by Regulating miR-223\/SIAH1 axis"],"prefix":"10.1210","volume":"163","author":[{"given":"Meng-yu","family":"Jing","sequence":"first","affiliation":[{"name":"Department of Reproductive Endocrinology, Women\u2019s Hospital, Zhejiang University School of Medicine , Hangzhou, 310006 , PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai-di","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Reproductive Endocrinology, Women\u2019s Hospital, Zhejiang University School of Medicine , Hangzhou, 310006 , PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Reproductive Endocrinology, Women\u2019s Hospital, Zhejiang University School of Medicine , Hangzhou, 310006 , PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Reproductive Endocrinology, Women\u2019s Hospital, 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