The miR-17-92 Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence

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	The miR-17-92 Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence
	Hong, LX ; Lai, MY ; Chen, M ; Xie, CC ; Liao, R ; Kang, YJ ; Xiao, CC ; Hu, WY ; Han, JH ; Sun, PQ ; Han JH(韩家淮)
刊名	http://dx.doi.org/10.1158/0008-5472.CAN-10-1938
	2010-11-01
关键词	RAS-INDUCED SENESCENCE CELL-CYCLE ARREST TUMOR SUPPRESSION SOLID TUMORS EXPRESSION PATHWAYS PROTEIN KINASE TARGET CANCER
英文摘要	NIH [CA106768, CA131231, RR025744, AI041637, AI068896]; NSF China [30828019]; 973 program [2009CB522200]; NSFC [30830092]; In mammalian cells, activation of oncogenes usually triggers innate tumor-suppressing defense mechanisms, including apoptosis and senescence, which are compromised by additional mutations before cancers are developed. The miR-17-92 gene cluster, a polycistron encoding six microRNAs (miRNA), is frequently overexpressed in human cancers and has been shown to promote several aspects of oncogenic transformation, including evasion of apoptosis. In the current study, we show a new role of miR-17-92 in inhibiting oncogenic ras-induced senescence. Further dissection of the miRNA components in this cluster reveals that the miR-17/20a seed family accounts for this antisenescence activity. miR-17 and miR-20a are both necessary and sufficient for conferring resistance to ras-induced senescence by directly targeting p21(WAF1), a key effector of senescence. By contrast, these components are not essential for the ability of miR-17-92 to evade Myc-induced apoptosis. Moreover, disruption of senescence by miR-17-92 or its miR-17/20a components leads to enhanced oncogenic transformation by activated ras in primary human cells. Taken together with previous reports that miR-17-92 inhibits apoptosis by suppressing Pten via the miR-19 components, our results indicate that this miRNA cluster promotes tumorigenesis by antagonizing both tumor-suppressing mechanisms, apoptosis, and senescence, through the activities of different miRNA components encoded in this cluster. Cancer Res; 70(21); 8547-57. (C)2010 AACR.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65752]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Hong, LX,Lai, MY,Chen, M,et al. The miR-17-92 Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence[J]. http://dx.doi.org/10.1158/0008-5472.CAN-10-1938,2010.
APA	Hong, LX.,Lai, MY.,Chen, M.,Xie, CC.,Liao, R.,...&韩家淮.(2010).The miR-17-92 Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence.http://dx.doi.org/10.1158/0008-5472.CAN-10-1938.
MLA	Hong, LX,et al."The miR-17-92 Cluster of MicroRNAs Confers Tumorigenicity by Inhibiting Oncogene-Induced Senescence".http://dx.doi.org/10.1158/0008-5472.CAN-10-1938 (2010).