这篇论文报告了在一个完好的哺乳动物生理系统（小鼠皮肤）中所完成的首次全基因组活体“RNA干涉”（RNAi）筛选。以前在哺乳动物细胞中进行的RNAi扫描都限于培养的细胞。作者将在胚胎表皮正常生长中所涉及的基因与由Hras致癌基因驱动的异常细胞增殖所必需的基因进行了比较。他们所获得的值得注意的发现包括β-catenin在正常细胞生长中所起的一个负面作用，这与在由致癌基因驱动的生长中需要β-catenin形成对比。从这次筛选中所产生的表皮生长潜在生理调控因子的列表，为未来研究提供了一个丰富资源，也为皮肤癌治疗提供了可能的目标。（生物谷 Bioon.com）
生物谷推荐的英文摘要
Nature doi:10.1038/nature12464
RNAi screens in mice identify physiological regulators of oncogenic growth
Slobodan Beronja, Peter Janki, Evan Heller, Wen-Hui Lien, Brice E. Keyes, Naoki Oshimori & Elaine Fuchs
Tissue growth is the multifaceted outcome of a cell’s intrinsic capabilities and its interactions with the surrounding environment. Decoding these complexities is essential for understanding human development and tumorigenesis. Here we tackle this problem by carrying out the first genome-wide RNA-interference-mediated screens in mice. Focusing on skin development and oncogenic (HrasG12V-induced) hyperplasia, our screens uncover previously unknown as well as anticipated regulators of embryonic epidermal growth. Among the top oncogenic screen hits are Mllt6 and the Wnt effector β-catenin, which maintain HrasG12V-dependent hyperproliferation. We also expose β-catenin as an unanticipated antagonist of normal epidermal growth, functioning through Wnt-independent intercellular adhesion. Finally, we validate functional significance in mouse and human cancers, thereby establishing the feasibility of in vivo mammalian genome-wide investigations to dissect tissue development and tumorigenesis. By documenting some oncogenic growth regulators, we pave the way for future investigations of other hits and raise promise for unearthing new targets for cancer therapies.
