Lin28 promotes transformation and is associated with advanced human malignancies

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dc.contributor.authorViswanathan, S.
dc.contributor.authorPowers, J.
dc.contributor.authorEinhorn, W.
dc.contributor.authorHoshida, Y.
dc.contributor.authorNg, T.
dc.contributor.authorToffanin, S.
dc.contributor.authorO'Sullivan, M.
dc.contributor.authorLu, J.
dc.contributor.authorPhilips, L.
dc.contributor.authorLockhart, V.
dc.contributor.authorSha, S.
dc.contributor.authorTanwar, P.
dc.contributor.authorMermel, C.
dc.contributor.authorBeroukhim, R.
dc.contributor.authorAzam, M.
dc.contributor.authorTeixeira, J.
dc.contributor.authorMeyerson, M.
dc.contributor.authorHughes, T.
dc.contributor.authorLlovet, J.
dc.contributor.authorMullighan, C.
dc.contributor.authoret al.
dc.date.issued2009
dc.description.abstractMultiple members of the let-7 family of miRNAs are often repressed in human cancers1,2, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc3,4. However, the mechanism by which let-7 miRNAs are co-ordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature miRNAs5–8, suggesting that their overexpression might promote malignancy through repression of let-7. Here we show that LIN28 and LIN28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency approx.15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. LIN28 and LIN28b facilitate cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28 and LIN28B with poor clinical prognosis.
dc.description.statementofresponsibilitySrinivas R Viswanathan... Timothy P Hughes... et al.
dc.identifier.citationNature Genetics, 2009; 41(7):843-U109
dc.identifier.doi10.1038/ng.392
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/57148
dc.language.isoen
dc.publisherNature Publishing Group
dc.source.urihttps://doi.org/10.1038/ng.392
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectNeoplasms
dc.subjectCarcinoma, Hepatocellular
dc.subjectLiver Neoplasms
dc.subjectCell Transformation, Neoplastic
dc.subjectRNA-Binding Proteins
dc.subjectDNA-Binding Proteins
dc.subjectMicroRNAs
dc.subjectGene Expression Regulation, Neoplastic
dc.titleLin28 promotes transformation and is associated with advanced human malignancies
dc.typeJournal article
pubs.publication-statusPublished

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