Abstract
Hepatitis C virus (HCV) is involved in the initiation and progression of liver fibrosis by regulating genes encoding host proteins. However, the underlying mechanism of HCV-induced liver fibrosis is still to be determined. Reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed to investigate the effect of HCV infection on the expression of the cellular microRNA miR-16 and its target genes encoding hepatocyte growth factor (HGF) and Smad7 in patients infected with HCV and in a liver cell line, QSG-7701, transfected with Ad-HCV, a recombinant adenovirus construct for expression of the HCV core protein. Regulation of HGF and Smad7 expression by miR-16 was assessed using luciferase reporter construct assays and miR-16 mimic transfection. Interferon-α (IFN-α) was used to verify the alteration of gene expression induced by HCV in QSG-7701 cells. Here, we found that miR-16 levels were increased in patients with HCV infection and were correlated with HGF and Smad7 expression levels in patients with HCV infection. Furthermore, HGF and Smad7 were predicted by bioinformatics analysis to be targets of miR-16. Upregulation of miR-16 and decreased HGF and Smad7 expression were still shown in QSG-7701 cells infected with Ad-HCV. Additionally, interferon-α (IFN-α) could reverse the changes in gene expression induced by HCV infection. These results suggest that the upregulation of miR-16 expression induced by HCV infection is a novel mechanism that contributes to downregulation of HGF and Smad7 in the development of liver fibrosis.
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Acknowledgments
Bin Zhu conceived and designed the experiments, Bin Zhu and Guang-wen Zhang analyzed the data. Bin Zhu and Xiao-xia Wei wrote the first draft of the manuscript. Tian-Bao Wang, Yan-cai Zhou, and A-min Liu contributed to the writing of the manuscript. Bin Zhu, Xiao-xia Wei, Tian-Bao Wang, Yan-cai Zhou, A-min Liu, and Guang-wen Zhang agree with manuscript results and conclusions. All authors reviewed and approved of the final manuscript.
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Zhu, B., Wei, Xx., Wang, Tb. et al. Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7. Arch Virol 160, 2043–2050 (2015). https://doi.org/10.1007/s00705-015-2474-3
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DOI: https://doi.org/10.1007/s00705-015-2474-3