Lin28 promotes transformation and is associated with advanced human malignancies.

Publication Type:

Journal Article

Source:

Nature genetics, Volume 41, Issue 7, p.843-8 (2009)

Keywords:

2009, Animals, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Transformation, Neoplastic, Center-Authored Paper, Clinical Research Division, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, MICE, MICRORNAS, Neoplasms, RNA-Binding Proteins, Shared Resources, Specimen Processing Core Facility

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.