瘤转化驱动DNA甲基化损失和转录元素位点的转录激活
Tomas Kanholm1,2,3, Uzma Rentia1,2, Melissa Hadley1,2
1The George Washington University Cancer Center (GWCC), Washington, DC.
Cancer research
|May 30, 2023
概括
移植元素 (TE) 在癌症发展过程中被重新激活. 这项研究表明,随着细胞的转变,内源逆转录病毒被脱甲基化和转录,反映了癌症的进展.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
背景情况:
- 可转移元素 (TE) 通常在健康组织中通过DNA甲基化和基因素修饰来沉默.
- 在许多癌症中,TE表达升高,与全球基因组低甲基化相关.
研究的目的:
- 通过使纤维细胞细胞不朽化和转化来建模瘤发生.
- 在这些转化阶段调查TE的表观遗传和转录变化.
主要方法:
- 纤维细胞与瘤基因的连续转导 (hTERT,SV40,HRASR24C).
- 在每个转化阶段进行RNA测序和全基因组双硫酸盐测序.
- 对差异甲基化区域 (DMR) 和TE表达的分析.
主要成果:
- 随着转化,TE表达显著增加,特别是在最后阶段之后.
- 内源性逆转录病毒,特别是长端重复病毒 (LTRs),是受到最高调节的TE.
- 转基因的低甲基化逐渐发生,从永生化开始,持续到转化.
- 上调的TE显示一致的脱甲基化和增加的转录,与"癌症基因组图谱"数据集的发现一致.
结论:
- TE表达和甲基化的失调是致癌转化的标志.
- 脱甲基化和随后的TEs转录,特别是内源性逆转录病毒,是瘤发生过程中的关键事件.
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