结合体是MYC驱动癌症的治疗漏洞
Tiffany Y-T Hsu1,2,3,4, Lukas M Simon4, Nicholas J Neill1,4
1Verna &Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nature
|September 3, 2015
概括
MYC的过度表达会压力结合体,这是RNA处理的关键机制. 抑制结合体可选择性地伤害MYC驱动的癌细胞,从而提供新的治疗点.
科学领域:
- 癌症学
- 分子生物学
- 癌症遗传学
背景情况:
- MYC (c-MYC) 是人类癌症的常见驱动因素,但仍然难以抑制治疗.
- 致癌性MYC会增加RNA和蛋白质的合成,可能会对细胞机械造成负担.
- 负责RNA处理的spliceosome被研究为MYC驱动癌症的潜在目标.
研究的目的:
- 确定MYC驱动的癌症的新治疗点.
- 研究结合体在MYC驱动的瘤发生中的作用.
- 探索MYC和结合体组件之间的合成致死性.
主要方法:
- 在人类乳腺上皮细胞中确定BUD31为MYC合成致命基因.
- BUD31作为核心结合体组件的特征.
- 在MYC过度激活下对结合体功能进行体外和体内评估.
- 结合体组件的遗传和药物抑制.
主要成果:
- 在MYC过度表达细胞中,它的抑制是致命的.
- MYC过度激活会增加前体传递 RNA 的合成,从而压力结合体.
- 在MYC过活化的细胞中,支离子体抑制会导致全球性内核保留和mRNA前成熟的缺陷.
- 抑制结合体会影响依赖MYC的乳腺癌的存活率,瘤性和转移.
结论:
- 瘤性MYC会对结合体产生附带压力.
- 在MYC驱动的癌症中,spliceosome代表了一个新的治疗漏洞.
- 针对结合体组件为治疗侵袭性MYC依赖性恶性瘤提供了一个有希望的策略.
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