Nature：微小RNA可以抑制癌症生长
生物谷报道：来自Cold Spring Harbor实验室（CSHL）的一组由Lin He，Xingyue He以及Greg Hannon教授领导的科学家最近确认了一种微型RNA（miRNAs）能够使一种被称为p53的关键肿瘤抑制网络来有效的对抗癌症细胞的生长。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表示："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。"在CSHL今年早些时候发表在《自然》（Nature）上的文章中，科学家表示，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，就可以实现停止癌症细胞的生长，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。当时大部分人认为蛋白质是p53这种能力的关键，但是在发表在6月6日 的《自然》（Nature）上的文章中，小组确定了miRNA是造成p53这一抗癌能力的关键因素。
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。He表示："我们的研究对于更好的了解癌症阻碍机制以及如何更好利用p53杀死癌细胞很有帮助。"
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
原文出处：
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
相关基因：
Official Symbol Tp53 and Name: tumor protein p53 (Li-Fraumeni syndrome) [Homo sapiens]
Other Aliases: LFS1, TRP53, p53
Other Designations: p53 tumor suppressor; tumor protein p53
Chromosome: 17; Location: 17p13.1
Annotation: Chromosome 17, NC_000017.9 (7531641..7512463, complement)
MIM: 191170
GeneID: 7157
作者简介：
Gregory J. Hannon, Ph.D.
Cold Spring Harbor Laboratory
Cold Spring Harbor
Research Field: RNA Biology, Cancer Biology
Never one to be confined by the limits of existing technology, Gregory Hannon takes matters into his own hands, creating the tools he and his colleagues need to address important biological questions. Hannon is at the forefront of the field of RNA interference (RNAi), a powerful new tool for gene analysis and discovery. His initial interest in RNAi, he says, grew out of “an intense frustration with the toolkit that was available for perturbing gene expression in mammalian cells and animals.”
Hannon and his colleagues have harnessed RNAi, a naturally occurring process of gene regulation, to selectively turn off genes in living cells. Hannon uses the technique to study cancer development and to probe the mechanisms that make this method of gene control so effective. He also investigates the potential of small interfering RNAs (siRNAs) for cancer therapy.
Hannon discovered two enzymes at the heart of the RNAi mechanism: Dicer, which chews up large pieces of double-stranded RNA and converts them to the short bits known as siRNAs, and argonaute2 (“Slicer”), the central enzyme in the second step of RNA silencing—targeted cleavage of messenger RNA by siRNAs.
While RNAi has been a powerful tool in selectively turning off genes in many organisms, there have been challenges to using it in mammalian cells. Mammalian cells respond to double-stranded RNA as if they have been infected by a virus: shutting down all protein synthesis, not just that of the target gene, quickly resulting in death of the cell. Researchers had to modify the technique for use in mammalian cells, so Hannon’s laboratory developed strategies for using short hairpin RNAs (shRNAs) to stably silence genes. The technique could greatly simplify gene manipulation and discovery for many biomedical applications.
Using Hannon’s approach, researchers can switch off any combination of genes in mouse cells in a targeted or random fashion and then infer the function of a particular gene. By randomly switching off genes, researchers can select cells with interesting properties, such as improved response to cancer treatment, and identify potential targets for new therapies.
To Hannon, developing and disseminating technologies that will spur scientific discovery in diverse fields is as important as using those tools in his own laboratory. With Stephen J. Elledge, HHMI investigator at
Gregory J. Hannon received a B.A. in biochemistry and a Ph.D. in molecular biology at
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