Browse

Functional links between clustered microRNAs: Suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer

Cited 373 time in Web of Science Cited 385 time in Scopus
Authors
Kim, Young-Kook; Yu, Jieun; Han, Tae Su; Park, Seong-Yeon; Namkoong, Bumjin; Kim, Dong Hyuk; Hur, Keun; Yoo, Moon-Won; Lee, Hyuk-Joon; Yang, Han-Kwang; Kim, V. Narry
Issue Date
2009-04
Publisher
OXFORD UNIV PRESS
Citation
Nucleic Acids Research, Vol.37 No.5, pp.1672-1681
Abstract
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.
ISSN
0305-1048
Language
English
URI
https://hdl.handle.net/10371/77867
DOI
https://doi.org/10.1093/nar/gkp002
Files in This Item:
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse