MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-κB signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFβ and Wnt/β-catenin. Particularly, it activates Wnt/β-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis.
Polysaccharide CharacterizationImmunomodulatory activity
A B S T R A C TThe crude polysaccharide from the stem of Dendrobium officinale (DOP) was obtained by water extraction and ethanol precipitation. Two fractions of DOP, DOP-1 and DOP-2, were fractioned by DEAE cellulose and Sephacryl S-400 gel filtration column chromatography.Their molecular weights and monosaccharide compositions were studied. The immunomodulatory activity of DOP, DOP-1 and DOP-2 was evaluated with in vitro cell models.The results showed that the 533.7 kDa DOP-1 and 159.5 kDa DOP-2 were mainly composed of mannose and glucose. Both DOP and its purified fractions significantly (P < 0.05) promoted splenocyte proliferation, enhanced natural killer cell-mediated cytotoxicity, and increased the phagocytosis and nitric oxide production of macrophages. Moreover, these two fractions caused a significant (P < 0.05) stimulation of cytokine secretion of both splenocytes and macrophages. These findings suggest that Dendrobium officinale polysaccharides should be explored as novel potential immunomodulators.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.