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Genome-wide profiling using whole-genome sequencing, Circle-Seq, and RNA-Seq was performed on four pairs of primary and cisplatin-resistant cell lines. The study uncovered an ecDNA carrying HIF1A in SKOV3 cisR cells, linked to DNA repair, drug efflux, and epithelial–mesenchymal transition, and identified 161,062 eccDNAs with chromosome-specific differences.",{"@graph":69,"@context":127},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/characterization-of-extrachromosomal-circular-dna-in-primary-and-cisplatin-resistant-high-grade-serous-ovarian-cancer/372388/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/characterization-of-extrachromosomal-circular-dna-in-primary-and-cisplatin-resistant-high-grade-serous-ovarian-cancer/372388.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What question does the study address about eccDNA and cisplatin resistance in HGSOC?","Question",{"text":113,"@type":114},"The study investigates how extrachromosomal circular DNA contributes to cisplatin resistance mechanisms in high-grade serous ovarian cancer.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which experimental approaches were used to characterize eccDNA?",{"text":118,"@type":114},"Whole-genome sequencing, Circle-Seq, and RNA-Seq were used to map eccDNA distribution and related gene expression features in primary and cisplatin-resistant cell lines.",{"name":120,"@type":111,"acceptedAnswer":121},"What key eccDNA finding is reported in the SKOV3 cisR cell line?",{"text":122,"@type":114},"A large extrachromosomal circular DNA carrying HIF1A was identified, and it is described as regulating DNA repair, drug efflux, and epithelial–mesenchymal transition to support cisplatin resistance.",{"name":124,"@type":111,"acceptedAnswer":125},"How many eccDNAs were detected and what general size and distribution patterns were observed?",{"text":126,"@type":114},"Circle-Seq detected 161,062 eccDNAs; most were under 1000 bp and distributed across all chromosomes, with notable differences on chromosome 21 between primary and cisplatin-resistant lines.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},372388,1790226811,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":144,"language":145,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":146,"faqs":147,"seo_title":148,"seo_description":67,"update_tm":149,"read_time":36},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Article  \nCharacterization of Extrachromosomal Circular DNA in Primary and Cisplatin-Resistant High-Grade Serous Ovarian Cancer  \nYouya Wang 1, He Li 1, Qinglan Li 2,3, Yi Li 2,3, Hao Wu 1, Yan Ge 1, Xingnuo Zhu 1, Zhiguo Zheng 4,5, * and Zhongsheng Sun 1,2,3,4, *  \nAcademic Editor: Yutaka Suzuki  \nReceived: 20 March 2025  \nRevised: 22 April 2025  \nAccepted: 25 April 2025  \nPublished: 29 April 2025  \nCitation: Wang, Y.; Li, H.; Li, Q.; Li, Y.; Wu, H.; Ge, Y.; Zhu, X.; Zheng, Z.; Sun, Z. Characterization of Extrachromosomal Circular DNA in Primary and Cisplatin-Resistant High-Grade Serous Ovarian Cancer. Genes 2025, 16, 517. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/genes16050517](10.3390/genes16050517)  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China; [youya_wang@163.com](youya_wang@163.com) (Y.W.); [lihe2944964125@gmail.com](lihe2944964125@gmail.com) (H.L.); [wu_hao2021@163.com](wu_hao2021@163.com) (H.W.); [gy1978185574@163.com](gy1978185574@163.com) (Y.G.); [believe_my_ship@163.com](believe_my_ship@163.com) (X.Z.)  \n2 Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; [liqinglan@biols.ac.cn](liqinglan@biols.ac.cn) (Q.L.); [liyieebio@zju.edu.cn](liyieebio@zju.edu.cn) (Y.L.)  \n3 College of Life Sciences, University of the Chinese Academy of Sciences, Beijing 100049, China  \n4 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China  \n5 Zhejiang Cancer Hospital, Hangzhou 310022, China  \n* Correspondence: [zhengzg@zjcc.org.cn](zhengzg@zjcc.org.cn) (Z.Z.); [sunzs@biols.ac.cn](sunzs@biols.ac.cn) (Z.S.)  \nAbstract: Background: Cisplatin resistance is a major cause of tumor recurrence and mortality in high-grade serous ovarian cancer (HGSOC) . Extrachromosomal circular DNA (eccDNA) has emerged as a critical factor in tumor evolution and drug resistance. However, the specific contribution of eccDNA to cisplatin resistance in HGSOC remains unclear. Methods: We performed whole-genome sequencing, Circle-Seq, and RNA-Seq in four pairs of primary and cisplatin-resistant (cisR) HGSOC cell lines to characterize genome-wide eccDNA distribution and features. Functional enrichment analyses were subsequently conducted on differentially expressed eccDNA-related genes. Results: In the SKOV3 cisR cell line, we identified a large extrachromosomal circular DNA (ecDNA) carrying the HIF1Agene, which regulates DNA repair, drug efflux, and epithelial–mesenchymal transition, contributing to cisplatin resistance. Using Circle-Seq, we detected a total of 161,062 eccDNAs, most of which were less than 1000 bp and distributed across all chromosomes. Notably, the number of eccDNAs on chromosome 21 differed significantly between the primary and cisR cell lines. Additionally, eccDNAs were predominantly located in non-coding repetitive elements. Functional analysis of eccDNA-related differentially expressed genes revealed that, compared to primary cell lines, cisR cell lines were associated with mitotic spindle assembly, regulation of vascular permeability, and cell differentiation. eccDNArelated genes involved in these pathways include MISP, WIPF1, RHOD, KRT80, and PLVAP. Conclusions: Our findings suggest that eccDNAs, particularly ecDNA amplifications like HIF1A, contribute significantly to cisplatin resistance mechanisms in HGSOC. These insights highlight eccDNA as a potential target for overcoming therapeutic resistance and improving treatment outcomes in ovarian cancer.  \nKeywords: HGSOC; cisplatin resistance; circle-Seq; eccDNA  \n1. Introduction  \nOvarian cancer is the most lethal gynecological malignancy, acco","cbCaigNi3YXU9flZ","https://ap.wps.com/l/cbCaigNi3YXU9flZ","pdf",3629362,16,"English","# Abstract\n# Introduction\n## Background on ovarian cancer and cisplatin resistance\n## Overview of extrachromosomal circular DNA (eccDNA)","[{\"question\":\"What question does the study address about eccDNA and cisplatin resistance in HGSOC?\",\"answer\":\"The study investigates how extrachromosomal circular DNA contributes to cisplatin resistance mechanisms in high-grade serous ovarian cancer.\"},{\"question\":\"Which experimental approaches were used to characterize eccDNA?\",\"answer\":\"Whole-genome sequencing, Circle-Seq, and RNA-Seq were used to map eccDNA distribution and related gene expression features in primary and cisplatin-resistant cell lines.\"},{\"question\":\"What key eccDNA finding is reported in the SKOV3 cisR cell line?\",\"answer\":\"A large extrachromosomal circular DNA carrying HIF1A was identified, and it is described as regulating DNA repair, drug efflux, and epithelial–mesenchymal transition to support cisplatin resistance.\"},{\"question\":\"How many eccDNAs were detected and what general size and distribution patterns were observed?\",\"answer\":\"Circle-Seq detected 161,062 eccDNAs; most were under 1000 bp and distributed across all chromosomes, with notable differences on chromosome 21 between primary and cisplatin-resistant lines.\"}]","Characterization of Extrachromosomal Circular DNA in Primary and Cisplatin-Resistant High-Grade Serous Ovarian Cancer | PDF",1790194399]