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

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  1. Human myotubularin-related protein 9 regulates ER-to-Golgi trafficking and modulates WNT3A secretion

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  2. A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis

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  3. Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme

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  1. The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells

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  2. Characterization of plasma lipidomics in adolescent subjects with increased risk for type 1 diabetes in the DiPiS cohort

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Long Noncoding RNAs in Diabetes and β-Cell Regulation

    Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

  4. Increased levels of inflammatory factors are associated with severity of polyneuropathy in type 1 diabetes

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  5. Self-reported immunity and opinions on vaccination of hospital personnel among paediatric healthcare workers in Denmark

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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.

Original languageEnglish
JournalExperimental Cell Research
Volume371
Issue number1
Pages (from-to)92-103
ISSN0014-4827
DOIs
Publication statusPublished - 1 Sep 2018

ID: 54880396