University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Centre for Cancer Research
  • Centre for Cancer Research - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Centre for Cancer Research
  • Centre for Cancer Research - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

    Thumbnail
    Download
    Published version (841.3Kb)

    Citations
    Scopus
    Web of Science
    Altmetric
    213
    187
    Author
    Cloonan, N; Brown, MK; Steptoe, AL; Wani, S; Chan, WL; Forrest, AR; Kolle, G; Gabrielli, B; Grimmond, SM
    Date
    2008-01-01
    Source Title
    Genome Biology
    Publisher
    BMC
    University of Melbourne Author/s
    Grimmond, Sean
    Affiliation
    Centre for Cancer Research
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Cloonan, N., Brown, M. K., Steptoe, A. L., Wani, S., Chan, W. L., Forrest, A. R., Kolle, G., Gabrielli, B. & Grimmond, S. M. (2008). The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition. GENOME BIOLOGY, 9 (8), https://doi.org/10.1186/gb-2008-9-8-r127.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258242
    DOI
    10.1186/gb-2008-9-8-r127
    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.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Centre for Cancer Research - Research Publications [45]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors