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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.identifier.citationNature Genetics, 2009; 41(7):843-U109-
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.publisherNature Publishing Group-
dc.subjectCell Line, Tumor-
dc.subjectCarcinoma, Hepatocellular-
dc.subjectLiver Neoplasms-
dc.subjectCell Transformation, Neoplastic-
dc.subjectRNA-Binding Proteins-
dc.subjectDNA-Binding Proteins-
dc.subjectGene Expression Regulation, Neoplastic-
dc.titleLin28 promotes transformation and is associated with advanced human malignancies-
dc.typeJournal article-
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]-
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]-
Appears in Collections:Animal and Veterinary Sciences publications
Aurora harvest 5

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