生物谷：在Cold Spring Harbor實(shí)驗(yàn)室（CSHL）今年早些時(shí)候發(fā)表在《自然》（Nature）上的文章中指出,，即使是在那些患有晚期癌癥的患者體內(nèi)，只要對(duì)之前被破壞的p53過程進(jìn)行重新的激活,，就可以實(shí)現(xiàn)抑制癌癥細(xì)胞生長,，甚至是通過激活周圍健康細(xì)胞的免疫反應(yīng)來徹底清除它們。但是近日發(fā)表在6月6日的《自然》（Nature）網(wǎng)絡(luò)版上的文章中指出,，miRNA卻是造成p53這一抗癌能力的關(guān)鍵因素,。
該研究是由來自（CSHL）的一組由Lin He，Xingyue He以及Greg Hannon教授領(lǐng)導(dǎo)的科學(xué)家完成的,。他們研究發(fā)現(xiàn),，一種微型RNA（miRNA）能夠促使p53的關(guān)鍵腫瘤抑制網(wǎng)絡(luò)來有效的對(duì)抗癌癥細(xì)胞的生長。大部分miRNA的表達(dá)會(huì)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(xì)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(xì)胞生長揭示了這一抗癌過程的全貌,。
來自CSHL癌癥中心的主任Scott Lowe表示：“在CSHL,，我們正在通過多個(gè)方面來增加對(duì)于p53過程的了解，因?yàn)樵谒械陌┌Y患者中,，幾乎都發(fā)生了這一過程的破壞,。” Hannon說：“通過和CSHL的多個(gè)其它研究實(shí)驗(yàn)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(xì)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(qiáng)有力的令人驚訝的原因。”當(dāng)時(shí)大部分人認(rèn)為蛋白質(zhì)是p53這種能力的關(guān)鍵,，而此次新非發(fā)現(xiàn)改變了他們對(duì)p53作用過程的看法,。He表示：“我們的研究對(duì)于更好的了解癌癥抑制機(jī)制以及如何更好利用p53殺死癌細(xì)胞很有幫助。”
英文原文鏈接：http://www.physorg.com/news100360397.html
原始出處:
Nature advance online publication 6 June 2007 | doi:10.1038/nature05939; Received 17 March 2007; Accepted 17 May 2007; Published online 6 June 2007
A microRNA component of the p53 tumour suppressor network
Lin He1,5, Xingyue He1,2,5, Lee P. Lim3, Elisa de Stanchina1,6, Zhenyu Xuan1, Yu Liang4, Wen Xue1, Lars Zender1, Jill Magnus3, Dana Ridzon4, Aimee L. Jackson3, Peter S. Linsley3, Caifu Chen4, Scott W. Lowe1, Michele A. Cleary3 & Gregory J. Hannon1
Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
Program in Genetics, Stony Brook University, Stony Brook, New York 11794, USA
Rosetta Inpharmatics, 401 Terry Avenue N., Seattle, Washington 98109, USA
Advanced Research & Technology, Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California 94404, USA
These authors contributed equally to this work.
Present address: Memorial Sloan-Kettering Cancer Center, 415 East 68th Street, New York, New York 10021, USA.
Correspondence to: Michele A. Cleary3Gregory J. Hannon1 Correspondence and requests for materials should be addressed to M.A.C. (Email: [email protected]) or G.J.H. (Email: [email protected]).
Abstract
A global decrease in microRNA (miRNA) levels is often observed in human cancers1, 2, indicating that small RNAs may have an intrinsic function in tumour suppression. To identify miRNA components of tumour suppressor pathways, we compared miRNA expression profiles of wild-type and p53-deficient cells. Here we describe a family of miRNAs, miR-34a–c, whose expression reflected p53 status. Genes encoding miRNAs in the miR-34 family are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo. Ectopic expression of miR-34 induces cell cycle arrest in both primary and tumour-derived cell lines, which is consistent with the observed ability of miR-34 to downregulate a programme of genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation.
