Characterization of Extrachromosomal Circular DNA in Primary and Cisplatin-Resistant High-Grade Serous Ovarian Cancer DOI Open Access

Youya Wang,

He Li, Qinglan Li

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 517 - 517

Published: April 29, 2025

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 critical factor evolution drug resistance. However, the specific contribution eccDNA to cisplatin HGSOC remains unclear. Methods: We performed whole-genome sequencing, Circle-Seq, RNA-Seq four pairs primary cisplatin-resistant (cisR) cell lines characterize genome-wide distribution features. Functional enrichment analyses were subsequently conducted on differentially expressed eccDNA-related genes. Results: In SKOV3 cisR line, we identified large extrachromosomal (ecDNA) carrying HIF1A gene, which regulates repair, efflux, epithelial–mesenchymal transition, contributing Using detected total 161,062 eccDNAs, most less than 1000 bp distributed across all chromosomes. Notably, number eccDNAs chromosome 21 differed significantly between lines. Additionally, predominantly located non-coding repetitive elements. analysis genes revealed that, compared lines, associated with mitotic spindle assembly, regulation vascular permeability, differentiation. involved these pathways include MISP, WIPF1, RHOD, KRT80, PLVAP. Conclusions: Our findings suggest that particularly ecDNA amplifications like HIF1A, contribute mechanisms HGSOC. These insights highlight potential target for overcoming therapeutic improving treatment outcomes cancer.

Language: Английский

Characterization of Extrachromosomal Circular DNA in Primary and Cisplatin-Resistant High-Grade Serous Ovarian Cancer DOI Open Access

Youya Wang,

He Li, Qinglan Li

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 517 - 517

Published: April 29, 2025

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 critical factor evolution drug resistance. However, the specific contribution eccDNA to cisplatin HGSOC remains unclear. Methods: We performed whole-genome sequencing, Circle-Seq, RNA-Seq four pairs primary cisplatin-resistant (cisR) cell lines characterize genome-wide distribution features. Functional enrichment analyses were subsequently conducted on differentially expressed eccDNA-related genes. Results: In SKOV3 cisR line, we identified large extrachromosomal (ecDNA) carrying HIF1A gene, which regulates repair, efflux, epithelial–mesenchymal transition, contributing Using detected total 161,062 eccDNAs, most less than 1000 bp distributed across all chromosomes. Notably, number eccDNAs chromosome 21 differed significantly between lines. Additionally, predominantly located non-coding repetitive elements. analysis genes revealed that, compared lines, associated with mitotic spindle assembly, regulation vascular permeability, differentiation. involved these pathways include MISP, WIPF1, RHOD, KRT80, PLVAP. Conclusions: Our findings suggest that particularly ecDNA amplifications like HIF1A, contribute mechanisms HGSOC. These insights highlight potential target for overcoming therapeutic improving treatment outcomes cancer.

Language: Английский

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