Chenyang Lu, Li Han, Xiaojuan Guo, Ruijuan Du, Hui Zhang, Kelei Guo, Yunfei Tu, Ruifang Li
{"title":"顺铂诱导的WWP1-eccDNA表达有助于卵巢癌抵抗。","authors":"Chenyang Lu, Li Han, Xiaojuan Guo, Ruijuan Du, Hui Zhang, Kelei Guo, Yunfei Tu, Ruifang Li","doi":"10.17219/acem/204077","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Multidrug resistance remains a major obstacle in the treatment of ovarian cancer (OC) patients. Recent research has underscored the critical role of extrachromosomal circular DNA (eccDNA) in tumor initiation and progression. However, there is limited comprehensive understanding of the role eccDNA plays in tumor resistance.</p><p><strong>Objectives: </strong>This study investigates the involvement of WWP1-eccDNA in the resistance mechanisms of OC.</p><p><strong>Material and methods: </strong>Human OC cells (SKOV3 and cisplatin-resistant SKOV3/DDP) were cultured and high-throughput sequencing was performed, leading to the identification of eccDNA in SKOV3/DDP cells. Female BALB/cA-nu nude mice with SKOV3 and SKOV3/DDP xenografts received cisplatin (5.5 mg/kg), hydroxyurea (50 mg/kg) or saline for 14 days, followed by tumor weight assessment. Digital droplet polymerase chain reaction (ddPCR) and real-time quantitative polymerase chain reaction (qPCR) were used to quantify WWP1-eccDNA, evaluating their sensitivity and accuracy. Linear DNA removal and BsmI digestion were tested to improve eccDNA detection.</p><p><strong>Results: </strong>WWP1-eccDNA was among the top upregulated eccDNA in SKOV3/DDP cells. Both cisplatin and hydroxyurea reduced tumor growth in mice, with cisplatin showing limited efficacy in resistant tumors. The ddPCR outperformed RT-qPCR in sensitivity, and linear DNA removal improved WWP1-eccDNA detection. WWP1-eccDNA levels were significantly elevated in SKOV3/DDP tumors. Treatment with cisplatin further increased its expression, whereas hydroxyurea led to a reduction in WWP1-eccDNA levels.</p><p><strong>Conclusions: </strong>WWP1-eccDNA is critical in OC resistance, with cisplatin treatment increasing WWP1-eccDNA levels, contributing to resistance. The ddPCR proves to be a superior method for eccDNA detection.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cisplatin-induced WWP1-eccDNA expression contributes to ovarian cancer resistance.\",\"authors\":\"Chenyang Lu, Li Han, Xiaojuan Guo, Ruijuan Du, Hui Zhang, Kelei Guo, Yunfei Tu, Ruifang Li\",\"doi\":\"10.17219/acem/204077\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Multidrug resistance remains a major obstacle in the treatment of ovarian cancer (OC) patients. Recent research has underscored the critical role of extrachromosomal circular DNA (eccDNA) in tumor initiation and progression. However, there is limited comprehensive understanding of the role eccDNA plays in tumor resistance.</p><p><strong>Objectives: </strong>This study investigates the involvement of WWP1-eccDNA in the resistance mechanisms of OC.</p><p><strong>Material and methods: </strong>Human OC cells (SKOV3 and cisplatin-resistant SKOV3/DDP) were cultured and high-throughput sequencing was performed, leading to the identification of eccDNA in SKOV3/DDP cells. Female BALB/cA-nu nude mice with SKOV3 and SKOV3/DDP xenografts received cisplatin (5.5 mg/kg), hydroxyurea (50 mg/kg) or saline for 14 days, followed by tumor weight assessment. Digital droplet polymerase chain reaction (ddPCR) and real-time quantitative polymerase chain reaction (qPCR) were used to quantify WWP1-eccDNA, evaluating their sensitivity and accuracy. Linear DNA removal and BsmI digestion were tested to improve eccDNA detection.</p><p><strong>Results: </strong>WWP1-eccDNA was among the top upregulated eccDNA in SKOV3/DDP cells. Both cisplatin and hydroxyurea reduced tumor growth in mice, with cisplatin showing limited efficacy in resistant tumors. The ddPCR outperformed RT-qPCR in sensitivity, and linear DNA removal improved WWP1-eccDNA detection. WWP1-eccDNA levels were significantly elevated in SKOV3/DDP tumors. Treatment with cisplatin further increased its expression, whereas hydroxyurea led to a reduction in WWP1-eccDNA levels.</p><p><strong>Conclusions: </strong>WWP1-eccDNA is critical in OC resistance, with cisplatin treatment increasing WWP1-eccDNA levels, contributing to resistance. The ddPCR proves to be a superior method for eccDNA detection.</p>\",\"PeriodicalId\":7306,\"journal\":{\"name\":\"Advances in Clinical and Experimental Medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Clinical and Experimental Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.17219/acem/204077\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Clinical and Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.17219/acem/204077","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Cisplatin-induced WWP1-eccDNA expression contributes to ovarian cancer resistance.
Background: Multidrug resistance remains a major obstacle in the treatment of ovarian cancer (OC) patients. Recent research has underscored the critical role of extrachromosomal circular DNA (eccDNA) in tumor initiation and progression. However, there is limited comprehensive understanding of the role eccDNA plays in tumor resistance.
Objectives: This study investigates the involvement of WWP1-eccDNA in the resistance mechanisms of OC.
Material and methods: Human OC cells (SKOV3 and cisplatin-resistant SKOV3/DDP) were cultured and high-throughput sequencing was performed, leading to the identification of eccDNA in SKOV3/DDP cells. Female BALB/cA-nu nude mice with SKOV3 and SKOV3/DDP xenografts received cisplatin (5.5 mg/kg), hydroxyurea (50 mg/kg) or saline for 14 days, followed by tumor weight assessment. Digital droplet polymerase chain reaction (ddPCR) and real-time quantitative polymerase chain reaction (qPCR) were used to quantify WWP1-eccDNA, evaluating their sensitivity and accuracy. Linear DNA removal and BsmI digestion were tested to improve eccDNA detection.
Results: WWP1-eccDNA was among the top upregulated eccDNA in SKOV3/DDP cells. Both cisplatin and hydroxyurea reduced tumor growth in mice, with cisplatin showing limited efficacy in resistant tumors. The ddPCR outperformed RT-qPCR in sensitivity, and linear DNA removal improved WWP1-eccDNA detection. WWP1-eccDNA levels were significantly elevated in SKOV3/DDP tumors. Treatment with cisplatin further increased its expression, whereas hydroxyurea led to a reduction in WWP1-eccDNA levels.
Conclusions: WWP1-eccDNA is critical in OC resistance, with cisplatin treatment increasing WWP1-eccDNA levels, contributing to resistance. The ddPCR proves to be a superior method for eccDNA detection.
期刊介绍:
Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly.
Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff.
Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj.
Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker.
The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition.
In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus.
Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.