Interferon-stimulated gene 15 in hepatitis B-related liver diseases

Hoàn, Nghiêm Xuân; Tong, Hoang Van; Giang, Đào Phương; Toàn, Nguyễn Lĩnh; Meyer, Christian G.; Bock, C.‐Thomas; Kremsner, Peter G.; Song, Lê Hữu; Velavan, Thirumalaisamy P.

doi:10.18632/oncotarget.11955

Cited by 12 publications

(11 citation statements)

References 47 publications

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“…Several IRF5 -modulated genes ( e.g ., ISGs and STATs) involved in the type I IFN signaling pathway are significantly over-expressed in response to viral infection[ 18 ]. This supports the findings of our study, namely that these SNPs may contribute to progression of HBV-related liver diseases through regulating IRF5 expression and subsequent activation of genes in the type I IFN signaling pathway like ISG15 as seen in our study[ 7 ]. Furthermore, although all four studied SNPs were not associated with HCC, the haplotype TCAT contributes to a decreased risk of HCC development in patients with chronic hepatitis B.…”

Section: Discussionsupporting

confidence: 92%

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

Sy¹,

Hoàn²,

Tong³

et al. 2018

WJG

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AIMTo investigate possible effects of IRF5 polymorphisms in the 3’ UTR region of the IFR5 locus on susceptibility to hepatitis B virus (HBV) infection and progression of liver diseases among clinically classified Vietnamese patients.METHODSFour IFR5 SNPs (rs13242262A/T, rs77416878C/T, rs10488630A/G, and rs2280714T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B (CHB). n = 99; liver cirrhosis (LC), n = 131; hepatocellular carcinoma (HCC), n = 149] and in 242 healthy controls by direct sequencing and TaqMan real-time PCR assays.RESULTSComparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262T and rs10488630G contributed to an increased risk of liver cirrhosis (LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients (OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups (LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin.CONCLUSIONOur study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.

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Section: Discussionsupporting

confidence: 92%

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

Sy¹,

Hoàn²,

Tong³

et al. 2018

WJG

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“…The interferon signalling pathway constitutes the first‐line defence against viral infections. The role of ISG‐15 in host defence against invading viral pathogens has previously been documented . In fact, our study proves the association of ISG‐15 with treatment response and suggests that the baseline of ISG‐15 expression is associated with treatment prediction.…”

Section: Discussionsupporting

confidence: 76%

“…The role of ISG-15 in host defence against invading viral pathogens has previously been documented. 58 In fact, our study proves the association of ISG-15 with treatment response and suggests that the baseline of ISG-15 expression is associated with treatment prediction. The ISG-15 is correlated with poor in vivo ISG response and poor viral kinetics resulting in poor virological outcomes to standard INFpeg-based therapy in patient infected with HCV.…”

Section: Treatment Type Analysis With the Genes Associated With Hcvsupporting

confidence: 61%

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

Sghaier

Brochot

Yacoubi-Loueslati

et al. 2019

Reviews in Medical Virology

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Summary HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.

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“…A number of enzymes involved in the ISGylation process, namely E3 ligases (HERC5 and EFP/TRIM25) and USP18 have been shown to be associated with cancers via ISGylation-dependent and -independent mechanisms [15][16][17][18]. We have previously shown that ISG15 expression is associated with HBV-related liver diseases, including HCC [23].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Enzymes involved in ISGylation and Ubiquitination in patients with hepatocellular carcinoma

Tong¹,

Hoàn²,

Binh³

et al. 2020

Int. J. Med. Sci.

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Background: ISGylation is the conjugation of ISG15 with target proteins. ISGylation occurs through an enzymatic cascade, which is similar to that of ubiquitination. Through ISGylation, ISG15 can bind to proteins involved in cell proliferation and differentiation, thus promoting genesis and progression of malignancies. The present study aims to investigate expression of genes involved in ISGylation and ubiquitination in patients with hepatocellular carcinoma and to correlate gene expression with clinical laboratory parameters of these patients. Methods: mRNA expression of genes encoding enzymes involved in the ISGylation process (EFP, HERC5, UBA1, UBC and USP18) was evaluated by quantitative real-time PCR in 38 pairs of tumour and adjacent non-tumour tissues from patients with hepatocellular carcinoma and correlated with distinct clinical laboratory parameters. Results: Relative mRNA expression of EFP, HERC5, UBA1 and USP18 was significantly higher in tumour tissues compared to adjacent non-tumour tissues (P=0.006; 0.012; 0.02 and 0.039, respectively). The correlation pattern of mRNA expression between genes in the tumours differed from the pattern in adjacent non-tumour tissues. Relative expression of EFP, HERC5 and UBA1 in adjacent non-tumour tissues was positively associated with direct bilirubin levels (Spearman's rho=0.31, 0.33 and 0.45; P=0.06, 0.05 and 0.01, respectively) and relative expression of USP18 in adjacent non-tumour tissues correlated negatively with ALT levels (Spearman's rho= -0.33, P=0.03). Conclusions: EFP, HERC5, UBA1, and USP18 genes are upregulated in tumour tissues of patients with HCC and, thus, may be associated with the pathogenesis of hepatocellular carcinoma.

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Interferon-stimulated gene 15 in hepatitis B-related liver diseases

Cited by 12 publications

References 47 publications

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

Upregulation of Enzymes involved in ISGylation and Ubiquitination in patients with hepatocellular carcinoma

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