引用次数达151的《Nature》文章调节p53的miRNA网络

　　

生物通报道，p53与microRNA都是近年来生命科学领域的热门研究课题，而关于二者间关联的研究也颇受瞩目，据最新的The Scientist报道，一篇发表于2007年的Nature文章就被引用151次，当属热门的miRNAs和p53的研究文章。

 

L. He et al., “A microRNA component of the p53 tumour suppressor network,” Nature, 447:1130–34, 2007. (Cited in 151 papers)

 

这篇文章有冷泉港实验室的分子生物学家Gregory Hannon研究小组完成，将正常的小鼠胚胎干细胞与p53突变的小鼠胚胎干细胞进行对比，结果发现一个参与p53调控的microRNA大家族，miR-34s家族。

 

如果miR-34s过度表达可能导致细胞生长停滞，种种数据表明，p53通过miR-34s家族式调控肿瘤抑制信号通路，miR34s是p53发挥作用的关键网络。

 

此外，2007年的夏天，还有其余4篇独立的文章证实p53通过miR-34s发挥作用，甚至调控细胞凋亡。

 

生物通推荐原文检索

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.

 

【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.