Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8962159 | Experimental Cell Research | 2018 | 39 Pages |
Abstract
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.
Keywords
HBSsilencer of death domainsSODDmiR-194HBV X proteincellular FLICE-inhibitory proteincFLIPCHBHBxThapsigarginHepG2HCCmitochondrial outer membrane permeabilizationNon-coding RNAtumor necrosis factor alphaApoptosisendoplasmic reticulumTNF-αMOMPchronic hepatitis BHBVhepatitis B virusHepatocellular carcinoma
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Authors
Kirstine Overgaard Nielsen, Kari Stougaard Jacobsen, Aashiq Hussain Mirza, Thilde Nordmann Winther, Joachim Størling, Dieter Glebe, Flemming Pociot, Birthe Hogh,