Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/57148
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Type: Journal article
Title: Lin28 promotes transformation and is associated with advanced human malignancies
Author: Viswanathan, S.
Powers, J.
Einhorn, W.
Hoshida, Y.
Ng, T.
Toffanin, S.
O'Sullivan, M.
Lu, J.
Philips, L.
Lockhart, V.
Sha, S.
Tanwar, P.
Mermel, C.
Beroukhim, R.
Azam, M.
Teixeira, J.
Meyerson, M.
Hughes, T.
Llovet, J.
Mullighan, C.
et al.
Citation: Nature Genetics, 2009; 41(7):843-U109
Publisher: Nature Publishing Group
Issue Date: 2009
ISSN: 1061-4036
1546-1718
Statement of
Responsibility: 
Srinivas R Viswanathan... Timothy P Hughes... et al.
Abstract: Multiple 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.
Keywords: Cell Line, Tumor; Animals; Humans; Mice; Neoplasms; Carcinoma, Hepatocellular; Liver Neoplasms; Cell Transformation, Neoplastic; RNA-Binding Proteins; DNA-Binding Proteins; MicroRNAs; Gene Expression Regulation, Neoplastic
RMID: 0020091048
DOI: 10.1038/ng.392
Appears in Collections:Animal and Veterinary Sciences publications

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