The work was supported by grants from Deutsche Forschungsgemeinschaft, French Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), and Spanish Ministry of Science and Innovation (SAF2010-21336 and BFU2010-20803).
Article first published online: 27 JUN 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 3, pages 1111–1112, 2 September 2011
How to Cite
Ehrhardt, M., Leidinger, P., Keller, A., Baumert, T., Díez, J., Meese, E. and Meyerhans, A. (2011), Profound differences of microRNA expression patterns in hepatocytes and hepatoma cell lines commonly used in hepatitis C virus studies. Hepatology, 54: 1111–1112. doi: 10.1002/hep.24366
Potential conflict of interest: Nothing to report.
- Issue published online: 25 AUG 2011
- Article first published online: 27 JUN 2011
- Accepted manuscript online: 18 APR 2011 08:31AM EST
- Manuscript Accepted: 1 APR 2011
To the Editor:
In their recent letter to the editor, Bensadoun et al. describe a divergent IL-28B (interleukin-28B) genotype of hepatoma cell lines including Huh7 and its derivatives.1 Because these cell lines are commonly used in cell culture studies of hepatitis C virus (HCV) and the IL-28B gene polymorphism is a predictive marker for the outcome of HCV infection, their observations emphasize the importance of cautiously interpreting infection studies performed in vitro. Here, we extend their conclusions and report profound differences in the microRNA (miRNA) expression between primary human hepatocytes (PHHs) and Huh7 cell lines.
Cellular miRNAs are key regulators in posttranscriptional regulation of gene expression. They can also directly participate in virus replication or act indirectly by determining the expression level of replication cofactors. To analyze whether the commonly used Huh7 cell lines differ in their miRNA expression patterns, we screened 883 human miRNAs using the Geniom Biochip miRNA Homo sapiens (febit holding gmbh, Heidelberg, Germany). PHHs isolated from human liver resections of two different patients were used as reference. Figure 1 and Supporting Table 1 show the profound differences not only between PHHs and hepatoma cell lines but also between the cell lines. Remarkably, the liver-specific miRNA122 that directly influences HCV replication both in cell culture and in infected chimpanzees2-4 was one of the most differentially expressed miRNAs. Furthermore, predictions of the gene targets of the miRNAs from Fig. 1A by the Genetrail program (freely accessible at http://genetrail.bioinf.uni-sb.de) identified a number of host proteins whose differential expression is known or expected to influence HCV replication (see Supporting Table 2 for the complete target list). Because studies on host factor requirements for virus replication nowadays involve small interfering RNA–mediated down-regulation of candidate proteins, and the level of knockdown is influenced by protein abundance and turnover and thus miRNA composition, one would expect that the respective experimental results would be influenced by the host cells used. The recent observations of nonoverlapping screening results for HCV host factors5 may well be related to corresponding miRNA differences in the host cells.
- 1Genetic background of hepatocyte cell lines: Are in vitro hepatitis C virus research data reliable? HEPATOLOGY 2011; doi:10.1002/hep.24278., , , , , .
- 2Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005; 309: 1577-1581., , , , .
- 3Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010; 327: 198-201., , , , , , et al.
- 4Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci U S A 2007; 104: 12884-12889., , , , , , et al.
- 5A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell Host Microbe 2009; 5: 298-307., , , , , , et al.
Michael Ehrhardt*, Petra Leidinger Ph.D., Andreas Keller Ph.D., Thomas F. Baumert Ph.D. §, Juana Díez Ph.D.¶, Eckart Meese Ph.D., Andreas Meyerhans Ph.D.* **, * Departments of Virology, Saarland University, Homburg, Germany, Human Genetics, Saarland University, Homburg, Germany, Institut National de la Santé et de la Recherche Médicale, Unité 748, § Université de Strasbourg, Strasbourg, France, ¶ Molecular Virology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, ** ICREA Infection Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Additional Supporting Information may be found in the online version of this article.
|HEP_24366_sm_SuppTable1.doc||1003K||Supporting Information Table 1.|
|HEP_24366_sm_SuppTable2.doc||946K||Supporting Information Table 2.|
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