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- Title
Lin28 promotes transformation and is associated with advanced human malignancies.
- Authors
Viswanathan, Srinivas R; Powers, John T; Einhorn, William; Hoshida, Yujin; Ng, Tony L; Toffanin, Sara; O'Sullivan, Maureen; Lu, Jun; Phillips, Letha A; Lockhart, Victoria L; Shah, Samar P; Tanwar, Pradeep S; Mermel, Craig H; Beroukhim, Rameen; Azam, Mohammad; Teixeira, Jose; Meyerson, Matthew; Hughes, Timothy P; Llovet, Josep M; Radich, Jerald; Mullighan, Charles G; Golub, Todd R; Sorensen, Poul H; Daley, George Q
- 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.
- Publication
Nature genetics, 2009, Vol 41, Issue 7, p843
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.392