Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China.
Clinical Research & Lab Center, The First People's Hospital of Kunshan, Kunshan, China.
Cancer Res Treat. 2021 Apr;53(2):506-527. doi: 10.4143/crt.2020.397. Epub 2020 Nov 16.
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.
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.
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.
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.
C5α 受体 1（C5ΑR1）与多种人类癌症的发展有关。然而，其是否参与乙型肝炎病毒（HBV）相关肝细胞癌（HCC）的发展尚不清楚。我们探讨了 C5ΑR1 在 HBV 相关肝癌细胞中的表达、生物学功能和相关机制。
检测了乙型肝炎病毒和乙型肝炎核心蛋白（HBc）介导的 C5ΑR1 在肝癌细胞中的表达。评估了核因子 кB（NF-κB）通路在 HBc 诱导的 C5ΑR1 表达中的作用。研究了 C5ΑR1 在 HBc 介导的细胞内信号通路激活、炎症细胞因子上调以及肝癌细胞生长和迁移中的作用。还测量了 C5α 在 C5ΑR1 介导的 HCC 发展中的作用。
HBV 阳性肝癌细胞中 C5ΑR1 的表达增加。HBc 依赖于 HBc 增加 C5ΑR1 在 mRNA 和蛋白水平上的表达。此外，HBc 可以通过 NF-κB 通路促进 C5ΑR1 的表达。基于 C5ΑR1，HBc 促进了 JNK 和 ERK 通路的激活以及白细胞介素-6 在肝癌细胞中的表达和分泌。此外，C5ΑR1 负责增强 HBc 介导的肝癌细胞的生长和迁移。除此之外，C5α 通过 C5AR1 可促进 HBc 阳性 HCC 的恶性发展。
我们为 HBc 介导的肝癌发生机制提供了新的见解。C5ΑR1 在 HBc 介导的肝癌细胞功能异常中具有重要作用，可能作为治疗 HBV 相关 HCC 的潜在靶点。
