Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||Lin28 promotes transformation and is associated with advanced human malignancies|
|Citation:||Nature Genetics, 2009; 41(7):843-U109|
|Publisher:||Nature Publishing Group|
|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|
|Appears in Collections:||Animal and Veterinary Sciences publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.