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  2. Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells

Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells

  • Cancer Res Treat. 2021 Apr;53(2):506-527. doi: 10.4143/crt.2020.397.
Fanyun Kong 1 Yukai Tao 1 2 Dongchen Yuan 1 Ning Zhang 1 Qi Li 1 Tong Yu 1 Xiaoying Yang 1 Delong Kong 1 Xiaohui Ding 1 Xiangye Liu 1 Hongjuan You 1 Kuiyang Zheng 1 3 Renxian Tang 1 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China.
  • 2 Clinical Research & Lab Center, The First People's Hospital of Kunshan, Kunshan, China.
  • 3 National Demonstration Center for Experimental Basic Medical Sciences Education, Xuzhou Medical University, Xuzhou, China.
Abstract

Purpose: C5α receptor 1 (C5ΑR1) 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 C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 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 C5α in the development of HCC mediated by C5AR1 was also measured.

Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1.

Conclusion: We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 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.

Keywords

C5ΑR1; Growth; HBc; Hepatitis B virus; Hepatocellular carcinoma; Migration.

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