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Unraveling Hepatitis C virus-induced biological circuits contributing to the development of hepatocellular carcinoma

Abstract : By combining a cell culture system of hepatocyte-like cells with purified hepatitis C virus (HCV), we effectively simulated chronic infection in vitro. We found this infection model induces a transcriptomic profile of chronic HCV patients at high risk of developing hepatocellular carcinoma (HCC). Using this model, we have uncovered the functional role of EGFR as a driver of the HCC risk signature and revealed candidate drivers of the molecular recalibration of hepatocytes leading to liver cancer. In an approach to study liver disease in vivo, we opted to screen for protein phosphatase expression in liver biopsies of chronic HCV patients. We observed a downregulation of PTPRD, a well-known tumor suppressor. We demonstrated that this effect is mediated by an increase in miR-135a-5p which targets PTPRD mRNA. Moreover, in silico analysis shows that PTPRD expression in adjacent liver tissue of HCC patients correlates with survival and reduced tumor recurrence after surgical resection.
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  • HAL Id : tel-01823837, version 1

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Nicolaas van Renne. Unraveling Hepatitis C virus-induced biological circuits contributing to the development of hepatocellular carcinoma. Virology. Université de Strasbourg, 2016. English. ⟨NNT : 2016STRAJ015⟩. ⟨tel-01823837⟩

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