Role of miR-143 targeting KRAS in colorectal tumorigenesis

Oncogene. 2009 Mar 12;28(10):1385-92. doi: 10.1038/onc.2008.474. Epub 2009 Jan 12.


Dysregulated expression of microRNAs (miRNAs) is associated with a variety of diseases, including colorectal cancer. By comparing more than 200 miRNAs in 13 pairs of matched colorectal cancer and normal adjacent tissue samples through qRT-PCR and microarray analysis, we found a widespread disruption of miRNA expression during colorectal tumorigenesis. In particular, among a panel of presumed targets generated by in silico analysis that may interact with these aberrantly expressed miRNAs, KRAS oncogene has been further experimentally validated as the target of miR-143. First, an inverse correlation between KRAS protein and miR-143 in vivo was found. Second, KRAS expression in Lovo cells was significantly abolished by treatment with miR-143 mimic, whereas miR-143 inhibitor increased KRAS protein level. Third, luciferase reporter assay confirmed that miR-143 directly recognize the 3'-untranslated region of KRAS transcripts. Four, Lovo cells treated with miR-143 inhibitor showed a stimulated cell proliferation, whereas miR-143 overexpression had an opposite effect. Finally, inhibition of KRAS expression by miR-143 inhibits constitutive phosphorylation of ERK1/2. Taken together, the present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / prevention & control*
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / analysis
  • MicroRNAs / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins p21(ras)
  • Reverse Transcriptase Polymerase Chain Reaction
  • ras Proteins / antagonists & inhibitors*


  • KRAS protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins