lncRNA基因PVT1的促进体是抑制瘤的DNA边界元素
Seung Woo Cho1, Jin Xu1, Ruping Sun2
1Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Cell
|May 8, 2018
概括
该PVT1促进体作为瘤抑制剂,独立于其lncRNA. 这种促进物的突变通过破坏MYC调节来增强癌症生长,突出显示癌症中的非编码调节元素.
科学领域:
- 遗传学
- 分子生物学
- 癌症研究
背景情况:
- 在癌症基因组中,非编码突变很常见,但难以解释.
- PVT1基因编码一种致癌的长非编码RNA (lncRNA),但与癌症相关的基因组变化表明其它作用.
- PVT1和MYC癌基因位于8q24染色体的附近.
研究的目的:
- 调查PVT1促进体的瘤抑制功能,独立于PVT1 lncRNA.
- 阐明PVT1促进体与MYC瘤基因表达之间的调节关系.
- 确定PVT1促进体突变在癌症发展中的作用.
主要方法:
- 通过CRISPR干扰 (CRISPRi) 抑制PVT1促进剂的活性.
- 对共享增强剂的促进者竞争的分析.
- 癌症基因组测序和基因组编辑验证.
主要成果:
- 促进PVT1的干扰增强了乳腺癌细胞的竞争和体内生长.
- PVT1促进剂与MYC促进剂在与PVT1内基增强剂的接触方面进行竞争.
- 这种竞争允许PVT1发起者通过暂停释放来调节MYC转录.
- 在癌症基因组中发现了PVT1促进基因突变,并表明它们促进癌细胞生长.
结论:
- 该PVT1促进体具有独立于PVT1 lncRNA的瘤抑制功能.
- PVT1和MYC之间的发起人竞争是一个关键的监管机制.
- 在PVT1促进体的突变有助于癌症的发展.
- lncRNA基因的调节序列代表了可能与疾病相关的DNA元素.
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