Search

Background: Synaptojanin 2 Binding Protein (SYNJ2BP) is essential to cell proliferation. Previous studies show that SYNJ2BP participates in sprouting angiogenesis, which plays an important part in several abnormal conditions including cancer. However, the activity of SYNJ2BP in hepatocellular carcinoma (HCC) has not been elucidated yet. Methods: Firstly, real-time PCR and western blotting (WB) were adopted to evaluate SYNJ2BP expressions in HCC tissues and HCC cell lines. Secondly, we did follow-up and prognostic study to explore the association of SYNJ2BP expression and HCC patients prognosis. Thirdly, we induced or silenced SYNJ2BP expression on selected HCC cell lines and explored the function of SYNJ2BP in vitro and in vivo. Lastly, we conducted Cignal Finder Cancer 10-Pathway Reporter Array in combination with loss- and gain-of-function assay to investigate potential mechanisms. Results: Through various techniques we found that SYNJ2BP was decreased in HCC tissues and HCC cell lines. The subsequent analysis showed that low expression of SYNJ2BP was associated with tumor size, tumor nodule number, vascular invasion, TNM stage and BCLC stage, and was an independent risk factor for survival of HCC. Later, the in vitro experiments demonstrated that SYNJ2BP inhibited HCC cells invasion, migration and proliferation, also the in vivo testing revealed that SYNJ2BP inhibited tumor growth and metastasis. Finally, we also uncovered that SYNJ2BP inhibited HCC growth and metastasis through activating DLL4-mediated Notch signaling pathway. Conclusions: Collectively, our data provide evidence that SYNJ2BP may act as a tumor suppressor during HCC development and could serve as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development.Methods: To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells.Results: H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway.Conclusions: The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers. [ABSTRACT FROM AUTHOR]