Ascites circRNA ASCOR Drives Platinum Resistance of High‐Grade Serous Ovarian Cancer by Facilitating RPA1 Nuclear Translocation
Source abstract
Abstract
ABSTRACT High‐grade serous ovarian carcinoma (HGSOC) remains the most lethal gynecologic malignancy, with platinum resistance posing the major therapeutic barrier. 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‐resistant 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‐dependent nuclear translocation, which recruits the RNA helicase DDX18, suppressing R‐loop formation. Meanwhile, the ASCOR‐RPA1‐DDX18 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‐driven pathway underlying platinum resistance in HGSOC, suggesting targeting ASCOR is a promising strategy for HGSOC treatment.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Circular RNAs in diseases · Extracellular vesicles in disease · Ferroptosis and cancer prognosis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
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 China
Department of Endocrinology Laboratory of Diabetes The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei China
Department of Obstetrics and Gynecology The First Affiliated Hospital of USTC The RNA Institute School of Basic Medical Sciences Center For Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Science and Medicine University of Science and Technology of China Hefei China
Department of Cardiology The First Affiliated Hospital of USTC Anhui Institute of Cardiovascular Diseases The RNA Institute Division of Life Sciences and Medicine University of Science and Technology of China Hefei China
Funding
National Natural Science Foundation of China · Fundamental Research Funds for the Central Universities
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