LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway

SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human cancers, where it has been assigned multiple functional roles. In this study, we report its association with the TGFβ1 signaling pathway, which promotes epithelial–mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in breast cancer tissues, in particular in primary invasive ductal carcinomas. Transcriptional activation of the SND1 gene was controlled by the TGFβ1/Smad pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter region contained several Smad-specific recognition domains (RD motifs), which were recognized and bound by the Smad complex that enhanced the transcriptional activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell adhesion, increased cell migration and invasion, and promoted metastasis. Overall, our results define a novel role for SND1 in regulating breast tumorigenesis and metastasis. Cancer Res; 75(7); 1275–86. ©2015 AACR.

CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis

Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells

Cancer stem-like cells directly participate in vasculogenic mimicry channels in triple-negative breast cancer

Human Tudor staphylococcal nuclease (Tudor-SN) is composed of four tandem repeats of staphylococcal nuclease (SN)-like domains, followed by a tudor and SN-like domain (TSN) consisting of a central tudor flanked by two partial SN-like sequences. The crystal structure of the tudor domain displays a conserved aromatic cage, which is predicted to hook methyl groups. Here, we demonstrated that the TSN domain of Tudor-SN binds to symmetrically dimethylarginine (sDMA)-modified SmB/B′ and SmD1/D3 core proteins of the spliceosome. We demonstrated that this interaction ability is reduced by the methyltransferase inhibitor 5-deoxy-5-(methylthio)adenosine. Mutagenesis experiments indicated that the conserved amino acids (Phe-715, Tyr-721, Tyr-738, and Tyr-741) in the methyl-binding cage of the TSN domain are required for Tudor-SN-SmB interaction. Furthermore, depletion of Tudor-SN affects the association of Sm protein with snRNAs and, as a result, inhibits the assembly of uridine-rich small ribonucleoprotein mediated by the Sm core complex in vivo. Our results reveal the molecular basis for the involvement of Tudor-SN in regulating small nuclear ribonucleoprotein biogenesis, which provides novel insight related to the biological activity of Tudor-SN.