BORIS促进治疗耐药癌细胞中的染色体调节相互作用
David N Debruyne1,2, Ruben Dries1,2,3, Satyaki Sengupta1,2
1Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature
|August 9, 2019
概括
CCCTC结合因子 (CTCF) 的同类BORIS (印记部位调节器的兄弟) 通过改变色素相互作用来驱动癌细胞的抵抗. 上调的BORIS促进超强增强剂和转录因子,支持恶性表型.
科学领域:
- 基因组学
- 癌症生物学
- 表观遗传学
背景情况:
- CCCTC结合因子 (CTCF) 将基因组组织成结构域并调节基因控制.
- 在癌症中中断CTCF结合可以激活瘤基因.
- 在癌症恶性中,BORIS (印记部位调节器的兄弟) 的作用尚不清楚.
研究的目的:
- 研究BORIS在癌症中的作用,特别是在抗ALK抑制的神经母细胞中.
- 阐明BORIS有助于恶性表型和耐药性的机制.
主要方法:
- 对抗ALK抑制的ALK突变,MYCN放大神经母细胞的分析.
- 研究基因表达,染色体相互作用和转录因子活性.
- 专注于MYCN,BORIS和染色体重塑之间的相互作用.
主要成果:
- 异常的BORIS上调促进了抗性神经母细胞中的染色体相互作用.
- 获得耐药性需要从MYCN依赖转变为BORIS依赖.
- 通过BORIS调节的染色质循环形成超强增强剂,驱动神经转录因子的异位表达,定义耐药性表型.
结论:
- 在促进特定癌症表型的调节性染色体相互作用方面,BORIS起着至关重要的作用.
- 这项研究确定了神经母细胞瘤中由BORIS驱动的抗药性新机制.
- 在某些癌症中,BORIS是克服耐药性的潜在治疗目标.
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