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Lin28 promotes transformation and is associated with advanced human malignancies.

Nature genetics | Jul 26, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19483683

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 RIS Download

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

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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:

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