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dc.contributor.authorCloonan, Nicoleen_US
dc.contributor.authorBrown, Mellissa K.en_US
dc.contributor.authorSteptoe, Anitaen_US
dc.contributor.authorWani, Shivangien_US
dc.contributor.authorChan, Wei Lingen_US
dc.contributor.authorForrest, Alistairen_US
dc.contributor.authorKolle, Gabrielen_US
dc.contributor.authorGabrielli, Brianen_US
dc.contributor.authorGrimmond, Seanen_US
dc.date.accessioned2017-04-24T14:54:55Z
dc.date.available2017-04-24T14:54:55Z
dc.date.issued2008en_US
dc.date.modified2009-11-13T06:38:31Z
dc.identifier.issn1474760Xen_US
dc.identifier.doi10.1186/gb-2008-9-8-r127en_AU
dc.identifier.urihttp://hdl.handle.net/10072/26679
dc.description.abstractBackground: 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.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent865950 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherBioMed Centralen_US
dc.publisher.placeUKen_US
dc.publisher.urihttp://genomebiology.com/en_AU
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom1en_US
dc.relation.ispartofpageto14en_US
dc.relation.ispartofissue8en_US
dc.relation.ispartofjournalGenome Biologyen_US
dc.relation.ispartofvolume9en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchGenome Structure and Regulationen_US
dc.subject.fieldofresearchcode270199en_US
dc.subject.fieldofresearchcode060407en_US
dc.titleThe miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transitionen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 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.en_AU
gro.date.issued2008
gro.hasfulltextFull Text


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