Synaptotagmin-7 is overexpressed in hepatocellular carcinoma and regulates hepatocellular carcinoma cell proliferation via Chk1–p53 signaling

Abstract

Background: Synaptotagmin-7 (Syt-7) is a member of the synaptotagmin (Syt) family, which plays an important role in many physiological and pathological processes. However, to the best of our knowledge, there is no study describing its function in tumors, particularly in hepatocellular carcinoma (HCC). Therefore, in this study, we examined the role of Syt-7 in HCC and attempted to elucidate its underlying mechanism. Materials and methods: We examined the expression levels of Syt-7 in HCC cell lines and normal hepatocytes by real-time quantitative polymerase chain reaction analysis. The effects of Syt-7 knockdown on in vitro cell growth were assessed by Celigo image cytometry, MTT assay, colony formation assay, and cell cycle analysis. In vivo tumorigenesis was evaluated using a nude mouse model. The underlying molecular mechanism was evaluated using a PathScan Stress Signaling Antibody Array. Results: Syt-7 mRNA levels were highly expressed in Huh-7 and Hep3B cells; moderately expressed in SMMC-7721, HepG2, and BEL-7402 cells; and lowly expressed in normal hepatocytes L-O2. Functional experiments demonstrated that Syt-7 knockdown significantly suppressed cell proliferation and induced cell cycle arrest by increasing phosphorylation of Chk1 and p53. Furthermore, Syt-7 knockdown remarkably reduced the growth of xenograft tumors in mice. Conclusion: The results of this study suggest that Syt-7 plays a vital role in tumorigenesis and in the development of HCC. Syt-7 can be used as a new diagnostic and therapeutic target in HCC.