- Hepatitis C virus infection stimulates transforming growth factor-β1 expression through up-regulating miR-192
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Ji Hyun Kim , Chang Ho Lee , Seong-Wook Lee
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J. Microbiol. 2016;54(7):520-526. Published online June 28, 2016
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DOI: https://doi.org/10.1007/s12275-016-6240-3
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 Abstract
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The objective of this study was to determine the molecular
mechanisms underlying chronic liver injury and fibrosis
caused by hepatitis C virus (HCV). This study revealed that
miR-192 expression was induced by HCV infection without
affecting viral replication. However, viral-induced miR-192
up-regulated transforming growth factor-β1 (TGF-β1) expression
in liver cells at transcriptional level. TGF-β1 stimulation
by HCV-induced miR-192 was caused through ZEB1
down-regulation and TGF-β1 increased miR-192 level via
positive feedback pathway. Increase in miR-192 expression
by HCV infection was due to HCV core protein released
and/or expressed by viral infection. TGF-β1 promoter activity
was also increased by HCV core protein in liver cells.
Taken together, HCV infection resulted in increased TGF-β1
transcription in hepatocytes through ZEB1 down-regulation
by HCV core-mediated miR-192 stimulation. Importantly,
miR-192 inhibition with anti-miR-192 rescued ZEB1 expression
down-regulated by HCV infection, thus reducing the
level of TGF-β1 expression increased by HCV infection in
hepatocytes. These results suggest a novel mechanism of
HCV-mediated liver fibrogenesis with miR-192 being a potential
molecular target to ameliorate viral pathogenesis.
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- The Role of MicroRNAs in Hepatitis C Virus Replication and Related Liver Diseases
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Chang Ho Lee , Ji Hyun Kim , Seong-Wook Lee
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J. Microbiol. 2014;52(6):445-451. Published online May 29, 2014
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DOI: https://doi.org/10.1007/s12275-014-4267-x
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971
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Abstract
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Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). However, only limited therapeutic options and no vaccines are currently
available against HCV infection. Recent studies of microRNAs (miRNAs), which are able to regulate HCV replication and its related liver diseases by directly interacting
with the HCV genome or indirectly controlling virus-associated host pathways, have broadened our understanding of the HCV life cycle. HCV utilizes host cellular miRNAs and modulates expression of miRNAs in infected hepatocytes for its infection and propagation. Moreover, such miRNAs directly or indirectly alter HCV replication efficiency and induce liver diseases including liver fibrosis, cirrhosis, or
HCC. Representatively, miR-122 directly modulates the HCV life cycle by increasing HCV translation and genomic RNA stability. Recently, a phase IIa clinical trial with miravirsen, an LNA form of antimiR-122 oligonucleotides, showed significant
reduction in serum HCV levels in patients chronically infected with HCV with no detectible evidence of resistance. In addition to miR-122, other miRNAs involved in
the regulation of HCV propagation could be targeted in strategies to modulate HCV replication and pathogenesis. In this review, we summarize the features of miRNAs critical for HCV replication and HCV-mediated liver abnormalities and briefly discuss their potential application as therapeutic reagents for the treatment of HCV infection and its related diseases.
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