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dc.contributor.authorCloonan, Nicole
dc.contributor.authorBrown, Mellissa K
dc.contributor.authorSteptoe, Anita L
dc.contributor.authorWani, Shivangi
dc.contributor.authorChan, Wei Ling
dc.contributor.authorForrest, Alistair Rr
dc.contributor.authorKolle, Gabriel
dc.contributor.authorGabrielli, Brian
dc.contributor.authorGrimmond, Sean M
dc.date.accessioned2017-05-03T16:58:19Z
dc.date.available2017-05-03T16:58:19Z
dc.date.issued2008
dc.date.modified2009-11-13T06:38:31Z
dc.identifier.issn1474-760X
dc.identifier.doi10.1186/gb-2008-9-8-r127
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent865950 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.publisher.placeUK
dc.publisher.urihttp://genomebiology.com/
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto14
dc.relation.ispartofissue8
dc.relation.ispartofjournalGenome Biology
dc.relation.ispartofvolume9
dc.rights.retentionY
dc.subject.fieldofresearchEnvironmental sciences
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchGenome structure and regulation
dc.subject.fieldofresearchInformation and computing sciences
dc.subject.fieldofresearchcode41
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode310508
dc.subject.fieldofresearchcode46
dc.titleThe miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/2.0
gro.rights.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.
gro.date.issued2008
gro.hasfulltextFull Text
gro.griffith.authorGabrielli, Brian
gro.griffith.authorForrest, Alistair RR.
gro.griffith.authorCloonan, Nicole


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