在DOX诱导的DNA损伤下,对HepG2细胞中eccDNA的识别和表征
Jinyuan Zhang1, Yuguo Li1, Weijie Chen1
1School of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
International journal of molecular sciences
|November 27, 2025
概括
在肝癌细胞中,DNA损伤增加了染色体外圆形DNA (eccDNA). 这些eccDNAs,特别是移动增强器eccDNAs (ME-eccDNAs),表现出改变的染色质和基因表达,影响癌症的进展.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 染色体外圆形DNA (eccDNA) 在癌症发育中起作用.
- 癌症中DNA损伤下eccDNA调节的机制尚不清楚.
研究的目的:
- 为了研究肝细胞癌 (HCC) 细胞中DNA损伤后的eccDNA变化和转录调节.
- 在基因毒性压力下描述eccDNA的生物发生和染色质特征.
主要方法:
- 在HepG2细胞中,多克索鲁比诱导的DNA损伤.
- 循环测量用于eccDNA分析.
- RNA-seq和ATAC-seq用于基因表达和染色体可访问性.
- Hi-C和H3K27ac ChIP-seq用于增强剂活性分析.
主要成果:
- DNA损伤显著增加了eccDNA的数量,长度和密度.
- 在eccDNA上的基因表达与损伤后的eccDNA复制数正相关.
- eccDNAs来自低甲基化,低GC含量区域.
- 移动增强器eccDNAs (ME-eccDNAs) 显示了增强的染色体相互作用和H3K27ac丰富.
结论:
- 在HCC中,DNA损伤驱动eccDNA生物发生,并改变它们的转录调节功能.
- ME-eccDNAs成为DNA损伤反应和癌症进展的关键参与者.
- 这项研究系统地阐明了肝癌中DNA损伤诱导的eccDNA机制.
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