miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis.
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.
Gebeshuber
Christoph A
CA
IMBA Vienna, Institute for Molecular Pathology, Dr Bohrgasse 3-5, 1030 Vienna, Austria. gebeshuber@imp.univie.ac.at
Zatloukal
Kurt
K
Martinez
Javier
J
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D051816:Tristetraprolin / Q000378:metabolism / Q000502:physiology*
D035683:MicroRNAs; D034741:RNA, Small Interfering; D051816:Tristetraprolin