這篇論文報(bào)告了在一個(gè)完好的哺乳動(dòng)物生理系統(tǒng)（小鼠皮膚）中所完成的首次全基因組活體“RNA干涉”（RNAi）篩選,。以前在哺乳動(dòng)物細(xì)胞中進(jìn)行的RNAi掃描都限于培養(yǎng)的細(xì)胞。作者將在胚胎表皮正常生長中所涉及的基因與由Hras致癌基因驅(qū)動(dòng)的異常細(xì)胞增殖所必需的基因進(jìn)行了比較。他們所獲得的值得注意的發(fā)現(xiàn)包括β-catenin在正常細(xì)胞生長中所起的一個(gè)負(fù)面作用,，這與在由致癌基因驅(qū)動(dòng)的生長中需要β-catenin形成對(duì)比。從這次篩選中所產(chǎn)生的表皮生長潛在生理調(diào)控因子的列表,，為未來研究提供了一個(gè)豐富資源,，也為皮膚癌治療提供了可能的目標(biāo),。（生物谷 Bioon.com）
生物谷推薦的英文摘要
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.
