Department of Microbiology & Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Korea.
BMB Rep. 2022 May;55(5):220-225. doi: 10.5483/BMBRep.2022.55.5.157.
Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis. [BMB Reports 2022; 55(5): 220-225].
肝细胞癌 (HCC) 是原发性肝癌的一种，是全球癌症相关死亡的主要原因之一。由于肝内和肝外转移，HCC 患者的预后较差。乙型肝炎病毒 (HBV) 感染是包括 HCC 在内的各种肝脏疾病的主要原因之一。在 HBV 基因产物中，HBV X 蛋白 (HBx) 在 HCC 的发展和转移中起重要作用。然而，HBx 诱导 HCC 转移的机制尚未阐明。在这项研究中，我们首次报道 HBx 与细胞因子信号转导抑制因子 1 (SOCS1) 相互作用，SOCS1 通过降解 NF-κB 的一个亚基 p65 来负调控 NF-κB。NF-κB 激活与上皮间质转化 (EMT) 相关的因子的转录，EMT 是与癌细胞侵袭和迁移相关的关键细胞过程。在这里，我们报告 HBx 与 SOCS1 发生物理结合，随后阻止了 p65 的泛素化，激活了 EMT 转录因子的转录，并增强了细胞迁移和侵袭能力，提示了 HBV 相关 HCC 转移的新机制。[BMB 报告 2022;55(5):220-225]。
