A microRNA component of the p53 tumour suppressor network
A microRNA component of the p53 tumour suppressor network
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DOI：
10.1038/nature05939
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发表时间：
2007-06-28
期刊：
影响因子：
64.8
通讯作者：
Hannon, Gregory J.
中科院分区：
文献类型：
--
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
在人类癌症中经常观察到微小RNA（miRNA）水平的全球性下降（1,2），这表明小RNA可能在肿瘤抑制中具有一种内在功能。为了鉴定肿瘤抑制通路的miRNA成分，我们比较了野生型和p53缺陷型细胞的miRNA表达谱。在此我们描述了一个miRNA家族，即miR - 34a - c，其表达反映了p53的状态。miR - 34家族中编码miRNAs的基因是p53的直接转录靶标，在体外和体内，它们受DNA损伤和致癌应激的诱导都依赖于p53。miR - 34的异位表达在原代细胞系和肿瘤来源的细胞系中都诱导细胞周期停滞，这与观察到的miR - 34下调促进细胞周期进展的基因程序的能力是一致的。p53网络通过多个转录靶标的协同激活来抑制肿瘤形成，并且miR - 34可能与其他效应物协同作用以抑制不适当的细胞增殖。
A global decrease in microRNA (miRNA) levels is often observed in human cancers(1,2), 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.