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Malignant ascites, a hallmark of advanced HGSOC, correlates with chemoresistance and poor prognosis, yet the contribution of ascites circRNAs in this process remains obscure. Here, we identify ASCOR, a circRNA upregulated in ascites small extracellular vesicles (sEVs) from platinum\u2010resistant HGSOC patients, predicts poor survival. ASCOR promotes platinum resistance in vitro and in vivo by enhancing cell viability, reducing apoptosis, and alleviating DNA damage, with effects also transferred via sEVs. Mechanistically, ASCOR binds RPA1 and facilitates its NUP153\u2010dependent nuclear translocation, which recruits the RNA helicase DDX18, suppressing R\u2010loop formation. Meanwhile, the ASCOR\u2010RPA1\u2010DDX18 axis activates PI3K\/Akt signaling to promote platinum resistance. Targeting ASCOR with antisense oligonucleotides reverses chemoresistance in mouse models. Our study unveils an ascites circRNA\u2010driven pathway underlying platinum resistance in HGSOC, suggesting targeting ASCOR is a promising strategy for HGSOC treatment.<\/jats:p>","DOI":"10.1002\/advs.202518922","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:12:27Z","timestamp":1770905547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ascites circRNA ASCOR Drives Platinum Resistance of High\u2010Grade Serous Ovarian Cancer by Facilitating RPA1 Nuclear Translocation"],"prefix":"10.1002","volume":"13","author":[{"given":"Hanyuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Core Facility Center The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui 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