HBx-Induced NF-κB Signaling in Liver Cells Is Potentially Mediated by the Ternary Complex of HBx with p22-FLIP and NEMO

Lim, Keo-Heun; Choi, Hyo Sun; Park, Yong Kwang; Park, Eun-Sook; Shin, Gu Choul; Kim, Doo Hyun; Ahn, Seung Ho; Kim, Kyun-Hwan

doi:10.1371/journal.pone.0057331

Cited by 28 publications

(25 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies have reported on the mechanisms responsible for HBX-mediated activation of the NF-κB pathway. It is reported that HBX can enhance the activation of NF-κB pathway via interaction with several intracellular proteins including AIB1 [30], p22-FLIP [31], NEMO [31], TBK1 [32], and VCP [33]. Besides, HBX has been demonstrated to activate NF-κB signaling pathway dependently on other signaling pathways such as PI3-K and Notch 1 [34–36].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Kong

Zhou

et al. 2016

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundInterleukin-7 receptor (IL-7R) is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC) are still unclear.MethodsGene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV) plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX). The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues. The role of NF-κB and Notch1 pathways in HBX-mediated expression of IL-7R in hepatoma cells was examined. Activation of IL-7R downstream of intracellular signaling proteins AKT, JNK, STAT5, and the associated molecules CyclinD1 and matrix metalloproteinase-9 (MMP)-9, was assessed in HBX-positive cells with or without treatment with IL-7R short hairpin RNA (shRNA). Additionally, the role of IL-7R in HBX-mediated proliferation and migration of hepatoma cells was investigated.ResultsThe expression of IL-7R was increased in hepatoma cells transfected with HBV plasmids; HBX was responsible for the HBV-mediated upregulation of IL-7R. Compared to adjacent tissues, the expression of HBX and IL-7R was increased in HBV-related HCC tissues. Additionally, the relative expression levels of HBX were associated with IL-7R in HBV-related HCC tissues. The activation of NF-κB pathways and expression of Notch1 were increased in hepatoma cells transfected with HBX, and inhibition of NF-κB and Notch1 pathways significantly decreased HBX-mediated expression of IL-7R. The activation of AKT and JNK and the expression of CyclinD1 and MMP-9 were increased in HBX-positive cells. When cells were treated with IL-7R shRNA, the activation of AKT and JNK, as well as the expression of CyclinD1 and MMP-9, were significantly inhibited. Additionally, IL-7R was responsible for HBX-induced proliferation and migration ability of hepatoma cells.ConclusionsOur data demonstrate that HBX can upregulate IL-7R via NF-κB and Notch1 pathways to facilitate the activation of intracellular pathways and expression of associated molecules, and contribute to proliferation and migration of hepatoma cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Kong

Zhou

et al. 2016

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Tat also associates with IκBα and prevents its binding to the NF-κB complex. Hepatitis B virus X protein (HBx) physically associates with the cleaved p22 form of cFLIP (p22-FLIP) and NEMO to form a ternary complex [71], which is required for HBx-induced NF-κB activation. This result is consistent with that p22-FLIP associates with and activates IKKα/β to instigate NF-κB activation.…”

Section: Activation Of the Nf-κb Signaling Pathway By Viral Proteinsmentioning

confidence: 99%

Recent advances on viral manipulation of NF-κB signaling pathway

Zhao

Minassian

et al. 2015

Current Opinion in Virology

View full text Add to dashboard Cite

NF-κB transcription factors regulate the expression of hundreds of genes primarily involved in immune responses. Signaling events leading to NF-κB activation constitute a major antiviral immune pathway. To replicate and persist within their hosts, viruses have evolved diverse strategies to evade and exploit cellular NF-κB immune signaling cascades for their benefit. We summarize recent studies concerning viral manipulation of the NF-κB signaling pathway downstream of pattern recognition receptors. Signal transduction mediated by pattern recognition receptors is a research frontier for both infectious disease and innate immunology.

show abstract

“…In chronic low-grade inflammation, sustained overproduction of proinflammatory Angptl2 could contribute [17]. The regulatory X protein of hepatitis B (HBx) activates the transcription factors nuclear factor kappa beta (NF-κB), which promotes HBV replication [18,19]. Angptl2 also activates the integrin α5β1/Rac1/ NFκB-dependent pathway, subsequently resulting in transcription of several proinflammatory cytokines [20,21].…”

Section: Introductionmentioning

confidence: 99%

Determination of liver fibrosis stages in Egyptian chronic hepatitis B patients by a noninvasive tool

Serag¹,

Mohamed²,

Eysa³

et al. 2019

Turk J Med Sci

View full text Add to dashboard Cite

Background/aim: Hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF). The prognosis and management of patients with chronic hepatitis B virus depend on the amount and progression of liver fibrosis. Angiopoietin-like protein 2 (Angptl2) is not only a chronic inflammatory mediator, but also a tissue-remodeling factor. The aim of this study is to explore the predictive value of Angptl2 in different fibrosis stages in patients chronically infected with HBV.Materials and methods: Eighty patients with chronic HBV infection undergoing Fibroscan were included. Serum concentrations of Angptl2 were detected using a commercial ELISA kit.Results: Angptl2 levels were significantly associated with liver fibrosis stages (P = 0.02). The area under the curve (AUC) of Angptl2 for distinguishing patients who showed significant fibrosis (F2-F4) was 70.2%. Angptl2 with fibrosis-4 (FIB-4) and Angptl2 with AST/ platelets ratio (APRI) performed best with an AUC of 92.5%. Conclusion:In patients with chronic HBV infection, Angptl2 level represents a potential biomarker independently associated with fibrosis stages. The combination of Angptl2 with FIB-4 or Angptl2 with APRI performed better than the existing models for diagnosing significant fibrosis.

show abstract

HBx-Induced NF-κB Signaling in Liver Cells Is Potentially Mediated by the Ternary Complex of HBx with p22-FLIP and NEMO

Cited by 28 publications

References 48 publications

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Recent advances on viral manipulation of NF-κB signaling pathway

Determination of liver fibrosis stages in Egyptian chronic hepatitis B patients by a noninvasive tool

Contact Info

Product

Resources

About