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Background and Aims: Hepatitis C virus (HCV) infection is an important risk factor for the development of liver cancer. The HCV NS3 protein plays a key role in the virus life cycle and can affect normal cellular activities, such as cell proliferation, cell death, and cell signaling pathways. Moreover, it may influence malignancy development. Two cellular genes, heat shock protein 70 (HSP70) and Glypican3 (GPC3), that are assessed in this study, play important roles in the regulation of the cell signaling pathways, including cell proliferation. This study aimed to evaluate the effects of HCV NS3 protein on the expressions of these two genes in the Balb/C mouse model.Materials and Methods: This study was performed on three groups of male mice of Balb/C (n=8). The first group received NS3 plasmid, the second group received hepatitis B virus HBx plasmid, and the negative control group received distilled water. Two injections were administered via the tail vein, and after the last injection, RNA was extracted from the liver tissue. Next, the cDNA synthesis and real-time polymerase chain reaction for relevant genes were performed.Results: Findings revealed that the relative expression of the selected genes in the NS3 group was significant in comparison with the negative control group (P=0.0229 for GPC3 and 0.0020 for HSP70). However, there was no significant difference between the NS3 group and the HBx group (P=0.4516 for GPC3 and 0.6740 for HSP70).Conclusion: Results showed that NS3 protein may affect the increasing expression of the mentioned genes. Nevertheless, for more precise understanding, much more studies should be performed, such as evaluation of the effect of NS3 on other involved proteins in cell signaling pathways, studying other domains of NS3, performance of pathological and histological tests, usage of various experimental methods, assessment of the role of NS4A as a cofactor for NS3, and usage of vectors with more stability.

Effects of hepatitis C virus NS3 protein on expression of heat shock protein 70 and Glypican3 as the markers of hepatocellular carcinoma