生物谷報道:來自Cold Spring Harbor實驗室(CSHL)的一組由Lin He,,Xingyue He以及Greg Hannon教授領(lǐng)導(dǎo)的科學(xué)家最近確認了一種微型RNA(miRNAs)能夠使一種被稱為p53的關(guān)鍵腫瘤抑制網(wǎng)絡(luò)來有效的對抗癌癥細胞的生長,。來自CSHL癌癥中心的主任Scott Lowe表示:"在CSHL,我們正在通過多個方面來增加對于p53過程的了解,,因為在所有的癌癥患者中,幾乎都發(fā)生了這一過程的破壞,。"
Hannon表示:"通過和CSHL的多個其它研究實驗室的合作,,我們已經(jīng)發(fā)現(xiàn)p53過程不僅僅可以阻礙腫瘤細胞的生長,甚至是清除它們,,而且更重要的是我們發(fā)現(xiàn)了一些使得這一過程變得如此強有力的令人驚訝的原因,。"在CSHL今年早些時候發(fā)表在《自然》(Nature)上的文章中,科學(xué)家表示,,即使是在那些患有晚期癌癥的患者體內(nèi),,只要對之前被破壞的p53過程進行重新的激活,就可以實現(xiàn)停止癌癥細胞的生長,,甚至是通過激活周圍健康細胞的免疫反應(yīng)來徹底清除它們,。當時大部分人認為蛋白質(zhì)是p53這種能力的關(guān)鍵,但是在發(fā)表在6月6日的《自然》(Nature)上的文章中,,小組確定了miRNA是造成p53這一抗癌能力的關(guān)鍵因素,。
大部分miRNA的表達會被腫瘤抑制,這表明其中一些miRNA能阻止腫瘤形成,。通過比較多種組織中細胞miRNA的水平,,CSHL科學(xué)家發(fā)現(xiàn)了p53改變和一種miRNA——miR-34損失間的關(guān)系。p53利用miRNA阻止癌細胞生長揭示了這一抗癌過程的全貌,。He表示:"我們的研究對于更好的了解癌癥阻礙機制以及如何更好利用p53殺死癌細胞很有幫助,。"
FIGURE 1. Expression of miR-34 is correlated with p53 status in MEFs.
a, An unsupervised hierarchical clustering based on miRNA expression profiles in wild-type and p53-/- MEFs with the indicated additional genetic alteration. Two independently constructed cell lines (.1 and .2) were analysed in each case. The complete heat map (linear scale) is presented in Supplementary Fig. S1. b, Predicted gene structures for human mir-34a and mir-34b/c were generated by combining information from expressed sequence tag databases, CAGE databases and 5' rapid amplification of cDNA ends. Sequence conservation between human, mouse and rat are represented as the percentage of conservation in the Vista analysis shown in the lower panel. The promoter regions of mir-34a and mir-34b/c each contain a palindromic sequence (shown in blue) that matches the canonical p53 binding site. The green bar indicates a CpG island. kb, kilobase.
原文出處:
A microRNA component of the p53 tumour suppressor network
Lin He, Xingyue He, Lee P. Lim, Elisa de Stanchina, Zhenyu Xuan, Yu Liang, Wen Xue, Lars Zender, Jill Magnus, Dana Ridzon, Aimee L. Jackson, Peter S. Linsley, Caifu Chen, Scott W. Lowe, Michele A. Cleary & Gregory J. Hannon
doi:10.1038/nature05939
First paragraph | Full Text | PDF (440K) | Supplementary information