期刊
NUCLEIC ACIDS RESEARCH
卷 37, 期 5, 页码 1672-1681出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp002
关键词
-
资金
- Ministry of Education, Science and Technology of Korea [R16-2007-073-01000-0]
- The National R& D Program for Cancer Control by the Ministry of Health, Welfare and Family a. airs of Korea [0720090]
- BK21 Research Studentship
- The National Creative Research Initiatives from the Ministry of Education, Science and Technology of Korea [R16-2007-07301000-0]
microRNAs (miRNAs) play integral roles in diverse processes including tumorigenesis. miRNA gene loci are often found in close conjunction, and such clustered miRNA genes are transcribed from a common promoter to generate polycistronic primary transcript. The primary transcript (pri-miRNA) is then processed by two RNase III proteins to release the mature miRNAs. Although it has been speculated that the miRNAs in the same cluster may play related biological functions, this has not been experimentally addressed. Here we report that the miRNAs in two clusters (miR-106b93 25 and miR-222 221) suppress the Cip/Kip family members of Cdk inhibitors (p57(Kip2), p21(Cip1) and p27(Kip1)). We show that miR-25 targets p57 through the 3-UTR. Furthermore, miR-106b and miR-93 control p21 while miR-222 and miR-221 regulate both p27 and p57. Ectopic expression of these miRNAs results in activation of Cdk2 and facilitation of G1/S phase transition. Consistent with these results, both clusters are abnormally upregulated in gastric cancer tissues compared to the corresponding normal tissues. Ectopic expression of miR-222 cluster enhanced tumor growth in the mouse xenograft model. Our study demonstrates the functional associations between clustered miRNAs and further implicates that effective cancer treatment may require a combinatorial approach to target multiple oncogenic miRNA clusters.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据