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Lin28 promotes transformation and is associated with advanced human malignancies.


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.

Pubmed ID: 19483683


  • Viswanathan 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


Nature genetics

Publication Data

July 26, 2009

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 1 R01 DK076986-01
  • Agency: NIH HHS, Id: DP1 OD000256
  • Agency: NIH HHS, Id: DP1 OD000256-01
  • Agency: NICHD NIH HHS, Id: R01 HD052701
  • Agency: NICHD NIH HHS, Id: R01 HD052701-02
  • Agency: NIGMS NIH HHS, Id: T32 GM007753
  • Agency: NHLBI NIH HHS, Id: T32-HL 66987
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms
  • Mice
  • MicroRNAs
  • Neoplasms
  • RNA-Binding Proteins