Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model
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Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model. / Nielsen, Kirstine Overgaard; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain; Winther, Thilde Nordmann; Størling, Joachim; Glebe, Dieter; Pociot, Flemming; Hogh, Birthe.
In: Experimental Cell Research, Vol. 371, No. 1, 2018, p. 92-103.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model
AU - Nielsen, Kirstine Overgaard
AU - Jacobsen, Kari Stougaard
AU - Mirza, Aashiq Hussain
AU - Winther, Thilde Nordmann
AU - Størling, Joachim
AU - Glebe, Dieter
AU - Pociot, Flemming
AU - Hogh, Birthe
N1 - Copyright © 2018. Published by Elsevier Inc.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1016/j.yexcr.2018.07.044
DO - 10.1016/j.yexcr.2018.07.044
M3 - Journal article
C2 - 30059664
VL - 371
SP - 92
EP - 103
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -
ID: 201500214