The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition

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Title The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition
Author Cloonan, Nicole; Brown, Mellissa K; Steptoe, Anita L; Wani, Shivangi; Chan, Wei Ling; Forrest, Alistair Raymond Russell; Kolle, Gabriel; Gabrielli, Brian; Grimmond, Sean M
Journal Name Genome Biology
Year Published 2008
Place of publication UK
Publisher BioMed Central
Abstract Background: MicroRNAs are modifiers of gene expression, acting to reduce translation through either translational repression or mRNA cleavage. Recently, it has been shown that some microRNAs can act to promote or suppress cell transformation, with miR-17-92 described as the first oncogenic microRNA. The association of miR-17-92 encoded microRNAs with a surprisingly broad range of cancers not only underlines the clinical significance of this locus, but also suggests that miR-17-92 may regulate fundamental biological processes, and for these reasons miR-17-92 has been considered as a therapeutic target. Results: In this study, we show that miR-17-92 is a cell cycle regulated locus, and ectopic expression of a single microRNA (miR-17-5p) is sufficient to drive a proliferative signal in HEK293T cells. For the first time, we reveal the mechanism behind this response - miR-17-5p acts specifically at the G1/S-phase cell cycle boundary, by targeting more than 20 genes involved in the transition between these phases. While both pro- and anti-proliferative genes are targeted by miR-17-5p, pro-proliferative mRNAs are specifically up-regulated by secondary and/or tertiary effects in HEK293T cells. Conclusion: The miR-17-5p microRNA is able to act as both an oncogene and a tumor suppressor in different cellular contexts; our model of competing positive and negative signals can explain both of these activities. The coordinated suppression of proliferation-inhibitors allows miR-17-5p to efficiently de-couple negative regulators of the MAPK (mitogen activated protein kinase) signaling cascade, promoting growth in HEK293T cells. Additionally, we have demonstrated the utility of a systems biology approach as a unique and rapid approach to uncover microRNA function.
Peer Reviewed Yes
Published Yes
Publisher URI http://genomebiology.com/
Alternative URI http://dx.doi.org/10.1186/gb-2008-9-8-r127
Copyright Statement Copyright 2008 Forrest et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Volume 9
Issue Number 8
Page from 1
Page to 14
ISSN 1474-760X
Date Accessioned 2009-08-17
Language en_AU
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Genome Structure and Regulation; PRE2009-Biochemistry and Cell Biology
URI http://hdl.handle.net/10072/26679
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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