Hepatitis B virus X protein promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating SOCS1

Abstract

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.

Comprehensive analysis of the expression and prognosis for IQ motif-containing GTPase-activating proteins in hepatocellular carcinoma

“…Many studies and our PPI network and KEGG results suggest that the interaction between IQGAP1 and Rho family proteins plays a vital role in the initiation and progression of HCC, especially in HBV-induced HCC [3,11,32]. Chronic hepatitis B infection has long been considered the most prominent pathogenic factor in HCC, and the hepatitis B virus X protein (HBx) is thought to be oncogenic and promotes the progression of HCC [33,34]. Xu et al found that HBx enhanced proliferation and inhibited apoptosis of HCC cells and was accompanied by significantly higher expression and activity of CDC42 and IQGAP1 [11].…”

Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer

“…Hepatitis B virus (HBV) infection has been demonstrated to be an important risk factor for high-risk liver cancer (2). Multiple studies have reported that HBV contributes to the proliferation and metastasis of liver cells, playing a crucial role in the high recurrence and mortality of liver cancer (3)(4)(5). Despite improvements that have been made in surgical resection and transplantation, the prognosis of patients with liver cancer remains unsatisfactory with a 5-year survival rate of <50% (6,7).…”

KIAA0317 regulates SOCS1 stability to ameliorate colonic inflammation

“…Micro-RNA has been shown to regulate SOCS1 expression, leading to a pro-inflammatory colonic phenotype [11,12]. Viral protein during Hepatitis B infection interacts with SOCS1 and impairs its activity [13].…”

“…MicroRNA has been shown to regulate SOCS1 expression, leading to a pro‐inflammatory colonic phenotype [11,12]. Viral protein during Hepatitis B infection interacts with SOCS1 and impairs its activity [13]. Recent studies have noted that RNF7 affects SOCS1 protein stability in the context of renal carcinoma [14], and SOCS1 protein stability can be prolonged through de‐ubiquitination by JOSD1 [15] or interaction with the protein CUEDC2 in acute myeloid leukaemia [16].…”