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

• DOI: 10.1038/embor.2009.9
• Publication Date: 2009-02-27T10:22:10Z
• Authors: Christoph A Gebes...; Kurt Zatloukal; Javier Martinez
• Keywords: Tristetraprolin

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.