在各种细胞应力中解码lncRNAome揭示了核心p53-效应器泛癌抑制lncRNAs
Ramkrishna Mitra1, Clare M Adams1, Christine M Eischen1
1Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
Cancer research communications
|June 28, 2023
概括
研究人员确定了由p53调节的核心长非编码RNA (lncRNAs),可以抑制各种癌症和细胞类型的瘤. 这些p53向的lncRNAs影响癌细胞生长和患者的存活率.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 长非编码RNAs (lncRNAs) 在癌症中发挥作用,但它们的调节和功能通常是未知的.
- 瘤抑制剂p53是癌症的关键调节剂,但其直接转录标,包括lncRNAs,尚未完全表征.
研究的目的:
- 在多种癌症类型中识别和表征核心p53调节的lncRNAs.
- 研究这些lncRNAs在瘤抑制中的功能作用及其与患者存活率的关联.
主要方法:
- 综合计算和实验方法,包括泛癌RNAi/CRISPR查,基因组,表观遗传和表达特征 (单细胞RNA测序).
- 在各种细胞应激下对p53依赖的转录调节的分析.
- 使用独立数据集,患者队列和基于细胞的测试进行实验验证.
主要成果:
- 确定了一组由p53直接交换激活的核心 lncRNAs,跨越多种癌症类型和细胞应激.
- 这些lncRNAs始终抑制癌细胞存活和生长,并与患者存活率的改善有关.
- 发现一种特定的lncRNA,PTSL通过调节G2调节网络来抑制增殖并诱导G2细胞循环停止.
结论:
- 阐明了以前未知的,高可信度的p53向lncRNAs,它们作为瘤抑制剂起作用.
- 揭示了这些lncRNAs在p53介导的细胞循环调节中的作用及其对癌症进展和患者结局的影响.
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