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

• Published in: Hepatology (Baltimore, Md.) Vol. 53; no. 5; pp. 1476 - 1485
• Main Authors: Zhang, Xiaoyong, Zhang, Ejuan, Ma, Zhiyong, Pei, Rongjuan, Jiang, Min, Schlaak, Joerg F., Roggendorf, Michael, Lu, Mengji
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2011; Wiley; Wiley Subscription Services, Inc
• Subjects: Biological and medical sciences; Cell cycle; Cell Differentiation - genetics; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Hepatitis; Hepatitis B; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - physiology; Hepatocytes - cytology; Hepatology; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; MicroRNAs; MicroRNAs - physiology; Molecular and cellular biology; Virus Replication - genetics; Viruses; Virus; Hepadnaviridae; Gastroenterology; Orthohepadnavirus; Replication; Hepatitis B virus; Cell differentiation
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.24195

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;)