The HCV-Associated Hepatocarcinogenesis in Intracellular Low Viral Load Cells = The HCV-Associated Hepatocarcinogenesis in Intracellular Low Viral Load Cells

다국어 초록 (Multilingual Abstract)

Aims: There are differential viral load distribution in HCV infected liver tissues. We conduct the present study aimed to dissect the different viral load cells to investigate the viral-host resistance on the HCV asssoicated hepatocarcinogenesis.
Methods: The study was performed using a replicated in vitro HCV-fluorescence infection model to discuss HCV-high viral load (HVL) cells and the HCV-low viral load (LVL) cells by Flow sort system. The next generation RNA sequence and miRNA array were used to explore the gene profiles and miRNA expression on different HCV-viral load cell populations.
Results: The ROS indicator shows that the ROS abundantly in low viral load cells. The RNA-Seq analysis showed that significant enrichment in Cancer (P=5.00E-02 - 2.76E-04; 40 molecules) and a network of the Cellular Movement, Immune Cell Trafficking, Inflammatory Response (Score: 18) by IPA analysis. Protein analysis results confirmed the GADD45A and iNOS overexpression in the LVL cells which verified the oxidative stress qPCR array data in LVL cells. We also found the up-regulated Src oncoprotein expression and down-regulated E-cadherin expression in LVL cells. The miRNA array showed that miR-194, miR-192/215 and miR-10a were preferentially expressed in low viral load cells.
Conclusions: With our established cell sorting system, this study provided the gene network between viral and host cells resistance by different viral load cells. The findings show the activated oxidative stress related-gene expression in hepatocytes is associated with the HCV-infected epithelial-to-mesenchymal transition (EMT), providing an important link between HCV viral load and liver cancer. The miRNA-gene intergraded dada need further studies.