Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model

Journal Article · Mon Oct 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.07.044· OSTI ID:23082598

Nielsen, Kirstine Overgaard; Jacobsen, Kari Stougaard ^[1]; Winther, Thilde Nordmann ^[2]; Størling, Joachim ^[3]; Glebe, Dieter ^[4]; Pociot, Flemming ^[1]; Hogh, Birthe ^[1]

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1. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (Denmark)
2. Department of Pediatrics, Hvidovre Hospital, University of Copenhagen, Copenhagen (Denmark)
3. Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics E, Herlev and Gentofte Hospital, Herlev (Denmark)
4. Institute of Medical Virology, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Justus-Liebig University Giessen, Giessen (Germany)

Highlights: • Hepatitis B virus changes the expression of host microRNAs in HepG2 cells. • MiR-192 and miR-194 regulate apoptosis. • MiR-192 and miR-194 target the important apoptosis-regulators BIM and cFLIP. • Hepatitis B virus upregulates microRNAs that affect apoptosis in vitro. Chronic hepatitis B (CHB) infection increases the risk of developing severe liver disease including cirrhosis and hepatocellular carcinoma (HCC). As microRNAs may modulate host – virus interactions, we here investigated if hepatitis B virus (HBV) infection modulate microRNA expression using an in vitro HepG2 cell model system with inducible HBV replication. We found that HBV replication was associated with upregulation of miR-192-5p, miR-194-5p and miR-215-5p, of which miR-192-5p and miR-215-5p have identical seed sequences. Bioinformatics analyses revealed a significant enrichment of potential target genes involved in apoptosis signaling of all three microRNAs. In line with this, transfection with a mimic of miR-192-5p suppressed the protein level of pro-apoptotic BIM and reduced endoplasmic reticulum (ER) stress-induced apoptosis in HepG2 cells. In contrast, transfection with a mimic of miR-194-5p downregulated the anti-apoptotic proteins SODD and cFLIP, and sensitized HepG2 cells to both ER stress- and cytokine-induced apoptosis. In conclusion, our study suggests that HBV upregulates the expression of miR-192-5p and miR-194-5p in the host cell. These microRNAs target important apoptosis-regulatory proteins, and may thus contribute to the development of HBV-related liver disease.

• OSTI ID: 23082598
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 371; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
ENDOPLASMIC RETICULUM
ENRICHMENT
HEPATITIS
HEPATOMAS
IN VITRO
LIVER
LYMPHOKINES
VIRUSES