miR-10b targets Tiam1: implications for Rac activation and carcinoma migration

Charlotte M. Harwood Moriarty, University of Massachusetts Medical School
Bryan M. Pursell, University of Massachusetts Medical School
Arthur M. Mercurio, University of Massachusetts Medical School

Abstract

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.