B-Cell-Intrinsic Hepatitis C Virus Expression Leads to B-Cell-Lymphomagenesis and Induction of NF-κB Signalling

Kasama, Yuri; Mizukami, Tamio; Kusunoki, Hideki; Peveling‐Oberhag, Jan; Nishito, Yasumasa; Ozawa, Makoto; Kohara, Michinori; Mizuochi, Toshiaki; Tsukiyama-Kohara, Kyoko

doi:10.1371/journal.pone.0091373

Cited by 20 publications

(18 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The immune selection was performed using ChIP grade NF-κB antibody in combination with Protein G conjugated solid support matrix magnetic beads. This NF-κB antibody has been validated extensively in previous studies to detect NF-κB proteins in Western blots and immunohistochemistry assays 49–51 .…”

Section: Experimental and Analytical Methodsmentioning

confidence: 99%

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration

et al. 2016

View full text Add to dashboard Cite

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1h post PHx. This set was associated with regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1h binding targets showed ethanol-specific differential expression through 6h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

show abstract

Section: Experimental and Analytical Methodsmentioning

confidence: 99%

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration

et al. 2016

View full text Add to dashboard Cite

show abstract

“…NFκB [p65] has been linked to diffuse large B cell lymphoma in many publications. The activation of NF-κB is regulated by two distinct pathways termed the "canonical" and the "non-canonical" NF-κB signalling pathways [5], while the classical NF-κB activation pathway involves dimerization of p50 and p65.…”

Section: Nf-κb [Nuclear Factor Kappa-light-chain-enhancer Of Activatementioning

confidence: 99%

“…The expression of miRNAs is also known to involve NF-κB activation. For example, miR-125a and miR-125b, both of which are often duplicated and/or over expressed in DLBCL, were shown to activate NF-κB by targeting the A20 and NF-κB mediated dysregulation of miRNAs observed in lymphoma [5].…”

Section: Nf-κb [Nuclear Factor Kappa-light-chain-enhancer Of Activatementioning

confidence: 99%

Diagnostic and Prognostic Value of Nuclear Factor Kappa-B in Diffuse Large B Cell Lymphoma in Egyptian Patients with Hepatitis C Virus Genotype 4

Halawani¹,

Sordi²,

Aiad³

et al. 2019

AJMB

View full text Add to dashboard Cite

Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] positive genotype-4 and HCV negative diffuse large B-cell lymphoma [DLBCL] patients, aiming at identification of its differential expression and prognosis in DLBCL and its subtypes; GCB and ABC. This is to establish its relation to HCV infection and its role in lymphogenesis. Besides assessing the role of new directly acting antiviral drugs [Sofusbuvir/Ledipasvir] concomitantly administered to [CHOP] combination in HCV positive DLBCL. Subjects and Methods: NFκB [p65] expression was assessed using Anti-NFκB [p65] antibody semi-quantitative technique in 30 newly diagnosed DLBCL patients [HCV positive [n = 15], HCV negative [n = 15]. Results: NFκB [p65] expression was higher in the HCV positive DLBCL patients than their HCV negative counterpart, with a positive correlation with the viral load [r = 0.536, p = 0.088]. NFκB [p65] expression was significantly more frequently detected in the ABC subtype than GCB subtype [p = 0.04]. Patients who expressed NFκB [p65] had higher incidence of extranodal involvement, advanced stages, higher LDH levels and IPI score. Besides, the expression of NFκB [P65] revealed an inferior overall response [OR] [p = 0.044]. Higher complete response rates to CHOP concomitantly with antiviral [ledipasvir/sofosbuvir] were encountered in the HCV positive group. In HCV positive group, NFκB [P65] displayed a positive relationship with the viral load and liver enzymes [p = 0.04], besides an inverse relation with serum albumin. This raises the possibility that NFκB [p65] expression is suggestive of the hepatic necro-inflammation in HCV pa-How to cite this paper: El tients. The ABC group presented more in advanced stages than GCB. Higher frequency of the ABC subgroup exhibited intermediate to high viral load, while it was less in the GCB. A statistically significant difference was found in the NFκB [p65] positive patients as regards MUM1 expression among the two groups [p ≤ 0.001]. Double positive [CD10+, MUM1+] and triple negative [CD10-, BCL6-, MUM1-] cases were encountered in the HCV positive group, and were characterized with a high NFκB [p65] expression. Conclusion: NFκB [p65] is expressed in patients with DLBCL, more frequently in ABC than in GCB subtypes. Expression of NFκB [p65] is associated with poor response to therapy in DLBCL. The NFκB [p65] disclosed an increased expression in HCV positive DLBCL compared to HCV negative group. The viral load displayed a positive correlation with the NFκB [p65] expression. Simultaneous administration of DAAs in combination with CHOP disclosed a better response and high tolerability.

show abstract

“…However, as the majority of the data derives from in vitro or murine models [Feldmann et al 2006;Sene et al 2007;Ito et al 2011;Marcucci and Mele, 2011], further research is required. Gene expression profiling of lymphoma B cells from HCV-transgenic mice has demonstrated that both canonical and an alternative nuclear factor κB pathway as well as the downregulation of some microRNAs may lead to lymphomagenesis [Kasama et al 2014]. A reduced expression of miR-26b has been found in patients with HCV-positive splenic marginal zone lymphoma (SMZL) [Peveling-Oberhag et al 2012].…”

Section: What Evidence Comes From Epidemiological Studies Linking Nhlmentioning

confidence: 99%

Hepatitis C virus-associated B-cell non-Hodgkin’s lymphomas: what do we know?

Vannata

Arcaini

Zucca

2015

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

Abstract:Epidemiological studies have shown an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. There is, however, a great geographic variability and it remains unclear whether additional environmental and genetic factors are involved or whether the international discrepancies represent simply a consequence of the variable prevalence of HCV infection in different countries. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used and the year of publication. The most convincing evidence for a causal relationship comes from the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after successful HCV eradication with antiviral treatment. Yet, the molecular mechanism of HCV-induced lymphomagenesis are mainly hypothetical. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by the chronic viral infection. This review will summarize the current knowledge on HCV-associated lymphomas and their management.

show abstract

B-Cell-Intrinsic Hepatitis C Virus Expression Leads to B-Cell-Lymphomagenesis and Induction of NF-κB Signalling

Cited by 20 publications

References 72 publications

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration

Diagnostic and Prognostic Value of Nuclear Factor Kappa-B in Diffuse Large B Cell Lymphoma in Egyptian Patients with Hepatitis C Virus Genotype 4

Hepatitis C virus-associated B-cell non-Hodgkin’s lymphomas: what do we know?

Contact Info

Product

Resources

About