在受体调节的基因激活程序的ncRNA依赖机制
Liuqing Yang1,2, Chunru Lin1,2, Chunyu Jin1
1Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla 92093, USA.
Nature
|August 16, 2013
概括
两个长非编码RNAs (lncRNAs),PRNCR1和PCGEM1,在侵袭性前列腺癌中增强雄激素受体 (AR) 活性. 准这些lncRNA抑制了瘤生长,这表明它们是割抵抗的关键.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
背景情况:
- 已知长非编码RNAs (lncRNAs) 在细胞确定和组织稳态中的作用,但它们在基因转录中的功能尚不清楚.
- 雄激素受体 (AR) 调节前列腺癌细胞的身份和行为,在荷尔蒙耐药癌症中经常独立于连接体作用.
- PRNCR1和PCGEM1是侵袭性前列腺癌中过度表达的 lncRNA.
研究的目的:
- 研究 lncRNAs PRNCR1 和 PCGEM1 在前列腺癌进展中的作用.
- 要确定这些lncRNAs如何与雄激素受体相互作用.
- 探索针对这些lncRNAs在割抵抗性前列腺癌中的治疗潜力.
主要方法:
- 研究了PRNCR1和PCGEM1与雄激素受体的结合.
- 利用短发针RNA (shRNA) 来向这些lncRNA在抵抗割的前列腺癌细胞系中.
- 评估了lncRNA向对AR介导的基因激活,增殖和瘤异种移植生长 in vivo的影响.
主要成果:
- PRNCR1和PCGEM1连续与雄激素受体结合,增强依赖体和依赖体的AR介导基因激活和增殖.
- PRNCR1与乙化AR结合,DOT1L是PCGEM1对甲基化AR的招募所必需的.
- 通过Pygopus 2 PHD域识别蛋白质标记,PCGEM1促进了增强剂-促进剂循环.
- 用shRNA向这些lncRNA显著抑制瘤异种移植生长在割抵抗性前列腺癌模型.
- 这些lncRNAs是需要在抗性前列腺癌细胞中激活截断和全长AR的.
结论:
- 过度表达的lncRNAsPRNCR1和PCGEM1在增强AR信号和扩散在侵袭性和割抵抗性前列腺癌中发挥着关键作用.
- 这些lncRNAs对于抗性前列腺癌细胞中的联结体独立AR激活至关重要.
- 向PRNCR1和PCGEM1为抵抗割的前列腺癌提供了一个潜在的治疗策略.
相关概念视频
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
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