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

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, modulati...

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Autores principales: Han, Ning, Zhang, Qingbo, Tang, Xiaoqiong, Bai, Lang, Yan, Libo, Tang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221477/
https://www.ncbi.nlm.nih.gov/pubmed/37243268
http://dx.doi.org/10.3390/v15051182
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author Han, Ning
Zhang, Qingbo
Tang, Xiaoqiong
Bai, Lang
Yan, Libo
Tang, Hong
author_facet Han, Ning
Zhang, Qingbo
Tang, Xiaoqiong
Bai, Lang
Yan, Libo
Tang, Hong
author_sort Han, Ning
collection PubMed
description 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.
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spelling pubmed-102214772023-05-28 Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells Han, Ning Zhang, Qingbo Tang, Xiaoqiong Bai, Lang Yan, Libo Tang, Hong Viruses Article 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. MDPI 2023-05-17 /pmc/articles/PMC10221477/ /pubmed/37243268 http://dx.doi.org/10.3390/v15051182 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Ning
Zhang, Qingbo
Tang, Xiaoqiong
Bai, Lang
Yan, Libo
Tang, Hong
Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells
title Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells
title_full Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells
title_fullStr Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells
title_full_unstemmed Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells
title_short Hepatitis B Virus X Protein Modulates p90 Ribosomal S6 Kinase 2 by ERK to Promote Growth of Hepatoma Cells
title_sort hepatitis b virus x protein modulates p90 ribosomal s6 kinase 2 by erk to promote growth of hepatoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221477/
https://www.ncbi.nlm.nih.gov/pubmed/37243268
http://dx.doi.org/10.3390/v15051182
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