Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas.
Department of Protein Science, KTH Royal Institute of Technology, Science for Life Laboratories, Stockholm, Sweden.
J Cell Physiol. 2019 Dec;234(12):22220-22233. doi: 10.1002/jcp.28789. Epub 2019 May 8.
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.
miR-206 已知可抑制乳腺癌。然而，尽管它在乳腺干细胞中表达，但它在这些非肿瘤细胞中的功能尚不清楚。在这里，我们使用鼠乳腺分化模型 HC11、全基因组基因表达分析和功能测定来探索 miR-206 在未分化的、干细胞样乳腺细胞中的作用。我们描述了 miR-206 调节的基因图谱，并提出了一个网络，其中 miR-206 抑制肿瘤的发生。我们通过功能证明，非肿瘤干细胞样细胞中的 miR-206 诱导 G1-S 细胞周期停滞，并降低集落形成和上皮间质转化标志物。最后，我们表明添加 miR-206 可加速乳腺分化过程以及相关脂质的积累。我们得出结论，miR-206 影响信号通路网络，并作为非肿瘤干细胞样乳腺细胞中增殖、干细胞特性和乳腺细胞分化的调节剂。我们的研究为 miR-206 抑制乳腺癌的功能提供了广泛的见解。
