Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells.

Abstract

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), one of the most prevalent malignant tumors worldwide that poses a significant threat to human health. The multifunctional regulator known as Hepatitis B virus X-protein (HBx) interacts with host factors, modulating gene transcription and signaling pathways and contributing to hepatocellular carcinogenesis. The p90 ribosomal S6 kinase 2 (RSK2) is a member of the 90 kDa ribosomal S6 kinase family involved in various intracellular processes and cancer pathogenesis. At present, the role and mechanism of RSK2 in the development of HBx-induced HCC are not yet clear. In this study, we found that HBx upregulates the expression of RSK2 in HBV-HCC tissues, HepG2, and SMMC-7721 cells. We further observed that reducing the expression of RSK2 inhibited HCC cell proliferation. In HCC cell lines with stable HBx expression, RSK2 knockdown impaired the ability of HBx to promote cell proliferation. The extracellularly regulated protein kinases (ERK) 1/2 signaling pathway, rather than the p38 signaling pathway, mediated HBx-induced upregulation of RSK2 expression. Additionally, RSK2 and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were highly expressed and positively correlated in HBV-HCC tissues and associated with tumor size. This study showed that HBx upregulates the expression of RSK2 and CREB by activating the ERK1/2 signaling pathway, promoting the proliferation of HCC cells. Furthermore, we identified RSK2 and CREB as potential prognostic markers for HCC patients.

• Authors: Ning Han, Qingbo Zhang, Xiaoqiong Tang, Lang Bai, Libo Yan, Hong Tang
• Journal: Viruses (Viruses) Vol. 15 Issue 5 (05 17 2023) ISSN: 1999-4915 [Electronic] Switzerland
• PMID: 37243268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• hepatitis B virus X protein
• Protein Kinases
• Ribosomal Protein S6 Kinases, 90-kDa
• Viral Regulatory and Accessory Proteins

Topics

• Humans
• Carcinoma, Hepatocellular (pathology)
• Liver Neoplasms (pathology)
• Protein Kinases (metabolism)
• Ribosomal Protein S6 Kinases, 90-kDa (genetics, metabolism)
• Hep G2 Cells
• Viral Regulatory and Accessory Proteins (metabolism)
• Hepatitis B (complications)
• Hepatitis B virus (physiology)
• Cell Line, Tumor