Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1

Xiaoyong Zhang; Ejuan Zhang; Zhiyong Ma; Rongjuan Pei; Min Jiang; Joerg F. Schlaak; Michael Roggendorf; Mengji Lu

doi:10.1002/hep.24195

journal article May 01, 2011

Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1

Xiaoyong Zhang

Ejuan Zhang Zhiyong Ma

Rongjuan Pei

Min Jiang

Joerg F. Schlaak Michael Roggendorf Mengji Lu

Hepatology Vol. 53 No. 5 pp. 1476-1485 · Ovid Technologies (Wolters Kluwer Health)

View at Publisher Save 10.1002/hep.24195

Abstract

Abstract

MicroRNAs (miRNAs) are highly conserved small noncoding RNAs participating in regulation of various cellular processes. Viruses have been shown to utilize cellular miRNAs to increase their replication in host cells. Until now, the role of miRNAs in hepatitis B virus (HBV) replication has remained largely unknown. In this study, a number of miRNA mimics were transfected into hepatoma cell lines with HBV replication. It was noted that microRNA-1 (miR-1) transfection resulted in a marked increase of HBV replication, accompanied with up-regulated HBV transcription, antigen expression, and progeny secretion. However, bioinformatics and luciferase reporter analysis suggested that miR-1 may not target the HBV genome directly but regulate the expression of host genes to enhance HBV replication. Further studies showed that miR-1 was able to enhance the HBV core promoter transcription activity by augmenting farnesoid X receptor α expression. In addition, miR-1 arrested the cell cycle at the G1 phase and inhibited cell proliferation by targeting histone deacetylase 4 and E2F transcription factor 5. Analysis of the cellular gene expression profile indicated that miR-1 transfected hepatoma cells developed a differentiated phenotype of hepatocytes.

Conclusion:

MiR-1 regulates the expression of several host genes to enhance HBV replication and reverse cancer cell phenotype, which is apparently beneficial for HBV replication. Our findings provide a novel perspective on the role of miRNAs in host-virus interactions in HBV infection. (Hepatology 2011;)

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References

Details

Published: May 01, 2011
Vol/Issue: 53(5)
Pages: 1476-1485
License: View

Authors

X

Xiaoyong Zhang

Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen 518055, P. R. China

Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Organic‐Inorganic Composites College of Chemical Engineering Beijing University of Chemical Technology Beijing 100029 China

Cite This Article

Xiaoyong Zhang, Ejuan Zhang, Zhiyong Ma, et al. (2011). Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1. Hepatology, 53(5), 1476-1485. https://doi.org/10.1002/hep.24195

Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1

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