基于瘤学的体内RNAi屏幕可以识别肝癌中的瘤抑制剂
Lars Zender1, Wen Xue, Johannes Zuber
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Cell
|November 18, 2008
概括
研究人员使用小鼠模型和RNA干扰屏幕确定了13个瘤抑制基因,包括XPO4,这对癌症发展至关重要. 这种方法有助于功能地注释癌症基因组.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 癌症表现出显著的异质性,有许多乘客和驾驶员突变.
- 识别新的瘤抑制基因对于理解癌症的发展和治疗策略至关重要.
研究的目的:
- 功能性地识别与人类癌症相关的瘤抑制基因.
- 为了确定体内RNA干扰 (RNAi) 选用于癌症基因发现的可行性.
主要方法:
- 编译的短毛针RNAs (shRNAs) 池,针对在人类肝细胞癌中删除的基因的小鼠正义基因.
- 在马赛克小鼠模型中测试了shRNA池,以评估它们促进瘤发生的能力.
- 结合癌症基因组学,RNA干扰和马赛克小鼠模型用于功能基因注释.
主要成果:
- 删除特定的shRNA池在小鼠中显著加快了肝癌发生.
- 鉴定并验证了13个瘤抑制基因,其中12个以前与癌症无关.
- 发现了核出口蛋白XPO4及其基质EIF5A2,在人体瘤中被放大并促进肝细胞癌.
结论:
- 活体RNAi选是一种可行的方法,用于发现癌症相关的基因.
- 在小鼠模型中将基因组数据与功能屏幕结合起来,可以有效地注释癌症基因组.
- 新型瘤抑制基因,如XPO4,为癌症治疗提供了潜在的新标.
相关概念视频
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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