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Nat Genet DOI:10.1038/ng.392

Lin28 promotes transformation and is associated with advanced human malignancies.

Publication TypeJournal Article
Year of Publication2009
AuthorsViswanathan, SR, Powers, JT, Einhorn, W, Hoshida, Y, Ng, TL, Toffanin, S, O'Sullivan, M, Lu, J, Phillips, LA, Lockhart, VL, Shah, SP, Tanwar, PS, Mermel, CH, Beroukhim, R, Azam, M, Teixeira, J, Meyerson, M, Hughes, TP, Llovet, JM, Radich, J, Mullighan, CG, Golub, TR, Sorensen, PH, Daley, GQ
JournalNat Genet
Volume41
Issue7
Pages843-8
Date Published2009 Jul
ISSN1546-1718
KeywordsAnimals, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Transformation, Neoplastic, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, Mice, MicroRNAs, Neoplasms, RNA-Binding Proteins
Abstract

Multiple members of the let-7 family of miRNAs are often repressed in human cancers, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature miRNAs, 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 approximately 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.

URLhttp://dx.doi.org/10.1038/ng.392
DOI10.1038/ng.392
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/19483683?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID19483683
PubMed Central IDPMC2757943
Grant List1 R01 DK076986-01 / DK / NIDDK NIH HHS / United States
R01 HD052701-02 / HD / NICHD NIH HHS / United States
R01 HD052701 / HD / NICHD NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 DK076986 / DK / NIDDK NIH HHS / United States
DP1 OD000256 / OD / NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
T32-HL 66987 / HL / NHLBI NIH HHS / United States
DP1 OD000256-01 / OD / NIH HHS / United States