在急性白血病中对Notch调节的长非编码RNA进行全基因组映射和表征
Thomas Trimarchi1, Erhan Bilal2, Panagiotis Ntziachristos1
1Howard Hughes Medical Institute, Laura and Isaac Perlmutter Cancer Center, and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Pathology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Cell
|August 2, 2014
概括
长非编码RNAs (lncRNAs) 是T细胞急性淋巴细胞白血病 (T-ALL) 中瘤性Notch1信号的下游目标. 一种特定的lncRNA,LUNAR1,通过增强IGF1R信号传递来驱动T-ALL的生长.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 痕信号在发育过程中至关重要,在人类癌症中经常发生变化.
- 异常的Notch1信号驱动T细胞急性淋巴细胞白血病 (T-ALL) 的发生.
- 作为T-ALL中Notch信号的下游目标的长非编码RNAs (lncRNAs) 的作用尚不清楚.
研究的目的:
- 研究 lncRNA 基因作为T-ALL.中的致癌性Notch1的下游标.
- 通过Notch1.1调节的新型T-ALL特异性lncRNAs的识别.
- 为了确定在T-ALL生长中的Notch调节lncRNAs的功能作用.
主要方法:
- 转录组概况的整合与染色体状态映射.
- 对Notch1/Rpbjκ直接转录标的分析.
- 在体外和体外功能测试以评估T-ALL生长.
主要成果:
- 发现了许多T-ALL特异性lncRNA基因.
- 通过Notch1/Rpbjκ复合体直接控制的lncRNAs的识别.
- 证明LUNAR1,一个Notch调节的lncRNA,通过调节IGF1RmRNA并维持IGF1信号,促进T-ALL增殖.
结论:
- lncRNAs是T-ALL.中Notch信号通路的重要下游目标.
- 划分调节的lncRNAs,如LUNAR1,是T-ALL.中瘤原体状态的关键调节者.
- 针对 lncRNAs 可能为T-ALL提供新的治疗策略.
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