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Translational Regulation in Hepatocellular Carcinogenesis.

ABSTRACT: The mortality of hepatocellular carcinoma (HCC) is distributed unevenly worldwide. One of the major causes is hepatitis B or hepatitis C virus infection and the development and progression of liver cirrhosis. The carcinogenesis of HCC is among others regulated via the mTOR (mechanistic target of rapamycin) signaling pathway and represents a possible method of targeted treatment. The aim of our article was to address the most recent clinical advances and findings of basic studies on the mTOR signaling pathway and the involved factors. Risk factors play a key role in dysregulation of the signaling pathway, where both mTORCs are upregulated and protein synthesis is altered. eIFs and, to a lesser extent, eEFs play an essential role in this process. Whether the factor will be upregulated or downregulated, among others, depends on hepatitis B/C virus infection. The amount of a particular factor in a patient sample lets us know whether HCC recurrence will occur, what is the likelihood of chemoresistance, and what outcome is predicted for patients with an increased value. Our analysis shows that in addition to mTOR, eIF3, eIF4, and eIF5 play an important role, as they can serve as biomarkers for non- and virus-related HCC.

SUBMITTER: Bracic Tomazic S

PROVIDER: S-EPMC8523516 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Translational Regulation in Hepatocellular Carcinogenesis.

Bracic Tomazic Suzana S Schatz Christoph C Haybaeck Johannes J

Drug design, development and therapy 20211014

The mortality of hepatocellular carcinoma (HCC) is distributed unevenly worldwide. One of the major causes is hepatitis B or hepatitis C virus infection and the development and progression of liver cirrhosis. The carcinogenesis of HCC is among others regulated via the mTOR (mechanistic target of rapamycin) signaling pathway and represents a possible method of targeted treatment. The aim of our article was to address the most recent clinical advances and findings of basic studies on the mTOR sign ...[more]

PMID: 34703211

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Project description:AimIn recent years, studies have suggested that Epstein-Barr virus (EBV) is associated with HCC. The present study was to determine the prevalence of EBV in HCC patients, and whether EBV acted synergistically with hepatitis viruses in HCC carcinogenesis.MethodsLiver tissue 115 HCC patients and 26 non-carcinoma patients were studied. Polymerase chain reaction (PCR) was performed to detect EBV BamHI W DNA, EBV LMP1 DNA, HBV X DNA, and HBV S DNA. Reverse transcription PCR (RT-PCR) was performed to detect HCV RNA and HDV RNA. Immunohistochemistry was performed to detect LMP1, HBsAg, HBcAg and HCV. The positive ratios were compared between HCC group and control group by chi2 test.ResultsTotally, 78 HCC samples whose beta-globulin DNA was positively detected by amplified PCR were selected. PCR was performed in all cases for EBV DNA and HBV DNA. RT-PCR was performed in 18 cases for HCV RNA and HDV RNA. EBV BamHI W and EBV LMP1 were positive in 18 and 6 cases, respectively. HBV X gene and HBV S gene were positive in 42 and 27 cases respectively. HCV was positive in one of the 18 cases, and none was positive for HDV. The positive rates were 28.2% (22 of 78) for EBV DNA (BamHI W and/or LMP1) and 56.4% (44 of 78) for HBV DNA (X gene and/or S gene) respectively. In addition, 12 cases were positive for both EBV DNA and HBV DNA. Among the 26 cases in the control group, 2 cases were positive for EBV BamHI W, 4 positive for HBV X gene and 3 positive for HBV S gene. The positive rates were 8.0% (2 of 26) and 23.1% (6 of 26), respectively, for EBV DNA and HBV DNA. The result of DNA sequencing of BamHI W was 100% homologous with the corresponding sequence of B95-8. There was significant difference in EBV infection rate between HCC patients and controls (chi2 = 4.622, P<0.05). The difference in HBV infection rate was also significant (chi2 = 8.681, P<0.05). However, there was no obvious correlation between HBV and EBV in HCC patients (chi2 = 0.835, P>0.05). LMP1, HBV (HBsAg, HBcAg) and HCV were detected positively in 25, 45 and 6 of 78 cases of HCC tissues respectively. In the 26 control cases, the corresponding positive cases were 2, 4 and 0. The difference in EBV infection rate between HCC patients and control cases was statistically significant (chi2 = 6.02, P<0.05). The difference in HBV infection rate was also statistically significant (chi2 = 10.03, P<0.05). In the 25 cases with positive LMP1 expression, 6 were in the nuclei of tumor cells, 9 in the cytoplasm of tumor cells and 10 in mesenchymal lymphocyte cytoplasm.ConclusionThe existence of EBV infection in HCC tissues suggests that EBV may be involved in the hepatocellular carcinogenesis in China. HBV infection may be a major cause of HCC. There is no correlation between EBV and HBV in the development of HCC. The prevalence of HCV infection is low in our area, and HDV appears not to play a direct role in hepatocellular carcinogenesis.

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Translational Regulation in Hepatocellular Carcinogenesis.

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Translational Regulation in Hepatocellular Carcinogenesis.

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