Hepatitis C virus induced up-regulation of microRNA-27: a novel mechanism for hepatic steatosis

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DOIResolve DOI: http://doi.org/10.1002/hep.26634
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TypeArticle
Journal titleHepatology
ISSN0270-9139
Volume59
Issue1
Pages98108; # of pages: 11
AbstractMicroRNAs (miRNAs) are small RNAs that posttranscriptionally regulate gene expression. Their aberrant expression is commonly linked with diseased states, including hepatitis C virus (HCV) infection. Herein, we demonstrate that HCV replication induces the expression of miR-27 in cell culture and in vivo HCV infectious models. Overexpression of the HCV proteins core and NS4B independently activates miR-27 expression. Furthermore, we establish that miR-27 overexpression in hepatocytes results in larger and more abundant lipid droplets, as observed by coherent anti-Stokes Raman scattering (CARS) microscopy. This hepatic lipid droplet accumulation coincides with miR-27b's repression of peroxisome proliferator-activated receptor (PPAR)-α and angiopoietin-like protein 3 (ANGPTL3), known regulators of triglyceride homeostasis. We further demonstrate that treatment with a PPAR-α agonist, bezafibrate, is able to reverse the miR-27b-induced lipid accumulation in Huh7 cells. This miR-27b-mediated repression of PPAR-α signaling represents a novel mechanism of HCV-induced hepatic steatosis. This link was further demonstrated in vivo through the correlation between miR-27b expression levels and hepatic lipid accumulation in HCV-infected SCID-beige/Alb-uPa mice. Conclusion: Collectively, our results highlight HCV's up-regulation of miR-27 expression as a novel mechanism contributing to the development of hepatic steatosis.
Publication date
LanguageEnglish
AffiliationMedical Devices; National Research Council Canada
Peer reviewedYes
NPARC number21270437
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Record identifier418a6f6b-8d62-48da-ad74-7a4ac9da9798
Record created2014-02-11
Record modified2016-05-09
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