miR-10b targets Tiam1: implications for Rac activation and carcinoma migration
Department of Cancer Biology
3' Untranslated Regions; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Female; Genes, Reporter; Guanine Nucleotide Exchange Factors; inhibitors; Humans; Luciferases; MicroRNAs; Neoplasm Invasiveness; Neoplasms; Polymerase Chain Reaction; RNA, Neoplasm; rac GTP-Binding Proteins
Understanding the mechanisms by which specific microRNAs regulate cell migration and invasion is a timely and significant problem in cancer cell biology. miR-10b is of interest in this regard because its expression is altered in breast and other cancers. Our analysis of potential miR-10b targets identified Tiam1 (T lymphoma invasion and metastasis 1), a guanidine exchange factor for Rac. We demonstrate, using an miR-10b synthetic precursor, expression vector, and antisense oligonucleotide, that miR-10b represses Tiam1 expression in breast carcinoma cells and that it interacts with the 3'-UTR of Tiam1. Consistent with the involvement of Tiam1 in cell motility, we observed that miR-10b suppresses the ability of breast carcinoma cells to migrate and invade. Importantly, we demonstrate that miR-10b also inhibits Tiam1-mediated Rac activation. These data provide a mechanism for the regulation of Tiam1-mediated Rac activation in breast cancer cells and need to be considered in the context of other reported functions for miR-10b.
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Citation: Moriarty CH, Pursell B, Mercurio AM. miR-10b targets Tiam1: implications for Rac activation and carcinoma migration. J Biol Chem. 2010 Jul 2;285(27):20541-6. Epub 2010 May 5. Link to article on publisher's website