Hepatitis B Virus Core Protein Mediates the Upregulation of C5? Receptor 1 via NF-KB Pathway to Facilitate the Growth and Migration of Hepatoma Cells

Purpose C5 alpha receptor 1 (C5 alpha R1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods The expression of C5 alpha R1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor ?B (NF-kappa B) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5 alpha R1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5 alpha in the development of HCC mediated by C5AR1 was also measured. Results C5 alpha R1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5 alpha R1 at the mRNA and protein levels. Besides, HBc could promote C5 alpha R1 expression via the NF-kappa B pathway. Based on the C5 alpha R1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Further- more, C5 alpha R1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5 alpha could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5 alpha R1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.