miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis

EMBO Rep. 2009 Apr;10(4):400-5. doi: 10.1038/embor.2009.9. Epub 2009 Feb 27.

Abstract

Several microRNAs (miRNAs) have recently been described as crucial regulators of epithelial-to-mesenchymal transition (EMT) and metastasis. By comparing the expression profiles of miRNAs, we found upregulation of miR-29a in mesenchymal, metastatic RasXT cells relative to epithelial EpRas cells. Overexpression of miR-29a suppressed the expression of tristetraprolin (TTP), a protein involved in the degradation of messenger RNAs with AU-rich 3'-untranslated regions, and led to EMT and metastasis in cooperation with oncogenic Ras signalling. We also observed enhanced miR-29a and reduced TTP levels in breast cancer patient samples, indicating relevance for human disease. Previously, miR-29 family members were shown to have tumour-suppressive effects in haematopoietic, cholangiocytic and lung tumours. Therefore, miRNAs can act as either oncogenes or tumour suppressors, depending on the context.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mesoderm / metabolism
  • Mesoderm / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Mutagenesis, Site-Directed
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • RNA, Small Interfering
  • Tristetraprolin / metabolism
  • Tristetraprolin / physiology*

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • Tristetraprolin