Lin28 promotes transformation and is associated with advanced human malignancies.

Nat Genet
Authors
Keywords
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.

Year of Publication
2009
Journal
Nat Genet
Volume
41
Issue
7
Pages
843-8
Date Published
2009 Jul
ISSN
1546-1718
URL
DOI
10.1038/ng.392
PubMed ID
19483683
PubMed Central ID
PMC2757943
Links
Grant list
1 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