Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene

Cancer. 2011 Jan 1;117(1):86-95. doi: 10.1002/cncr.25522. Epub 2010 Aug 24.


Background: Tumor suppressor microRNA miR-145 is commonly down-regulated in colon carcinoma tissues, but its specific role in tumors remains unknown.

Methods: In this study, the authors identified the Friend leukemia virus integration 1 gene (FLI1) as a novel target of miR-145. FLI1 is involved in t(11;22)(q24:q12) reciprocal chromosomal translocation in Ewing sarcoma, and its expression appears to be associated with biologically more aggressive tumors.

Results: The authors demonstrated that miR-145 targets a putative microRNA regulatory element in the 3'-untranslated region (UTR) of FLI1, and its abundance is reversely associated with FLI1 expression in colon cancer tissues and cell lines. By using a luciferase/FLI1 3'-UTR reporter system, they found that miR-145 down-regulated the reporter activity, and this down-regulation was reversed by anti-miR-145. Mutation of the miR-145 microRNA regulatory element sequence in the FLI1 3'-UTR abolished the activity of miR-145. miR-145 decreased FLI1 protein but not FLI1 mRNA, suggesting a mechanism of translational regulation. Furthermore, the authors demonstrated that miR-145 inhibited cell proliferation and sensitized LS174T cells to 5-fluorouracil-induced apoptosis.

Conclusions: Taken together, these results suggest that miR-145 functions as a tumor suppressor by down-regulating oncogenic FLI1 in colon cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Computational Biology
  • Gene Expression Regulation
  • Gene Targeting*
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / pharmacology*
  • Protein Biosynthesis
  • Proto-Oncogene Protein c-fli-1 / genetics*
  • Proto-Oncogene Protein c-fli-1 / metabolism
  • Regulatory Sequences, Nucleic Acid


  • 3' Untranslated Regions
  • MIRN145 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Protein c-fli-1