536 Changes in NF-KB activation and iNOS and Mn-SOD gene expression during the progression to hepatocarcinoma in patients with chronic HCV infection

Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths, which is largely caused by virus infection. About 80% of the virus-infected people develop a chronic infection that eventually leads to liver cirrhosis and hepatocellular carcinoma (HCC). With approximately 71 million HCV chronic infected patients worldwide, they still have a high risk of HCC in the near future. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches. Hepatitis C virus (HCV) infection largely causes hepatocellular carcinoma (HCC) worldwide with 3 to 4 million newly infected cases diagnosed each year. It is urgent to explore its underlying molecular mechanisms for therapeutic treatment and biomarker discovery. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches.

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Enhanced Expression of Interferon-Regulated Genes in the Liver of Patients with Chronic Hepatitis C Virus Infection: Detection by Suppression-Subtractive Hybridization

Journal of Virology ◽

10.1128/jvi.75.3.1332-1338.2001 ◽

2001 ◽

Vol 75 (3) ◽

pp. 1332-1338 ◽

Cited By ~ 71

Author(s):

René Patzwahl ◽

Volker Meier ◽

Giuliano Ramadori ◽

Sabine Mihm

Keyword(s):

Gene Expression ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Subtractive Hybridization ◽

Hcv Infection ◽

Gene Encoding ◽

Enhanced Expression ◽

Chronic Hcv Infection ◽

Ifn Γ ◽

Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) infection causes acute and often also chronic liver disease. Worldwide, prevalence of infection is estimated to exceed that of human immunodeficiency virus infection fourfold. Because of the lack of appropriate animal models, knowledge of interactions between virus and host is still limited. Assumptions regarding pathogenesis or the activation status of innate antiviral host responses, for instance, derive mainly from clinical observations and from expression analyses of selected genes. To obtain a more objective insight into virus-host interrelationships, we used suppression-subtractive hybridization to compare gene expression in HCV-infected and non-HCV-infected liver tissues samples. Four differentially expressed genes were found: (i) the gamma interferon (IFN-γ)-inducible chemokine IP-10 gene; (ii) the IFN-α/β-inducible antiviral MxA gene; (iii) the gene encoding IFN-α/β-inducible p44, shown to be associated with ultrastructural cytoplasmic entities within hepatocytes of non-A, non-B hepatitis-infected chimpanzees; and (iv) the gene encoding IFN-α/β/γ-inducible IFI-56K, a protein recently shown to interact with the eukaryotic translation initiation factor eIF-3. Compared to hepatic gene expression in patients with liver diseases unrelated to viral infections, expression in patients with chronic HCV infection was up to 50-fold higher. While in patients with chronic HBV infection IP-10 was slightly activated as well, the IFN-α/β-regulated genes were not. Revealing a dominance of hepatic interferon-regulated processes in chronic HCV infection, data on the enhanced expression of the IFN-γ regulated IP-10 support earlier findings and may explain the composition of the hepatic cellular infiltrate. The data on enhanced expression of IFN-α/β inducible genes might be germane to therapeutic considerations.

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