生物谷：在Cold Spring Harbor实验室（CSHL）今年早些时候发表在《自然》（Nature）上的文章中指出，即使是在那些患有晚期癌症的患者体内，只要对之前被破坏的p53过程进行重新的激活，就可以实现抑制癌症细胞生长，甚至是通过激活周围健康细胞的免疫反应来彻底清除它们。但是近日发表在6月6日的《自然》（Nature）网络版上的文章中指出，miRNA却是造成p53这一抗癌能力的关键因素。
该研究是由来自（CSHL）的一组由Lin He，Xingyue He以及Greg Hannon教授领导的科学家完成的。他们研究发现，一种微型RNA（miRNA）能够促使p53的关键肿瘤抑制网络来有效的对抗癌症细胞的生长。大部分miRNA的表达会被肿瘤抑制，这表明其中一些miRNA能阻止肿瘤形成。通过比较多种组织中细胞miRNA的水平，CSHL科学家发现了p53改变和一种miRNA——miR-34损失间的关系。p53利用miRNA阻止癌细胞生长揭示了这一抗癌过程的全貌。
来自CSHL癌症中心的主任Scott Lowe表示：“在CSHL，我们正在通过多个方面来增加对于p53过程的了解，因为在所有的癌症患者中，几乎都发生了这一过程的破坏。” Hannon说：“通过和CSHL的多个其它研究实验室的合作，我们已经发现p53过程不仅仅可以阻碍肿瘤细胞的生长，甚至是清除它们，而且更重要的是我们发现了一些使得这一过程变得如此强有力的令人惊讶的原因。”当时大部分人认为蛋白质是p53这种能力的关键，而此次新非发现改变了他们对p53作用过程的看法。He表示：“我们的研究对于更好的了解癌症抑制机制以及如何更好利用p53杀死癌细胞很有帮助。”
英文原文链接：http://www.physorg.com/news100360397.html
原始出处:
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: michele_cleary@merck.com) or G.J.H. (Email: hannon@cshl.org).
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.
