SYNJ2BP inhibits tumor growth and metastasis by activating DLL4 pathway in hepatocellular carcinoma

Abstract

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.