A miR-206 regulated gene landscape enhances mammary epithelial differentiation

Abstract

miR-206 is known to suppress breast cancer. However, while it is expressed in mammary stem cells, its function in such nontumor cells is not well understood. Here, we explore the role of miR-206 in undifferentiated, stem-like mammary cells using the murine mammary differentiation model HC11, genome-wide gene expression analysis, and functional assays. We describe the miR-206-regulated gene landscape and propose a network whereby miR-206 suppresses tumor development. We functionally demonstrate that miR-206 in nontumor stem-like cells induces a G1–S cell cycle arrest, and reduces colony formation and epithelial-to-mesenchymal transition markers. Finally, we show that addition of miR-206 accelerates the mammary differentiation process along with related accumulation of lipids. We conclude that miR-206 impacts a network of signaling pathways, and acts as a regulator of proliferation, stemness, and mammary cell differentiation in nontumor stem-like mammary cells. Our study provides a broad insight into the breast cancer suppressive functions of miR-206.