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Review
. 2021 May 19;13(10):2485.
doi: 10.3390/cancers13102485.

HCV Proteins Modulate the Host Cell miRNA Expression Contributing to Hepatitis C Pathogenesis and Hepatocellular Carcinoma Development

Devis Pascut  1 , Minh Hoang  2 , Nhu N Q Nguyen  3 , Muhammad Yogi Pratama  1 , Claudio Tiribelli  1
Affiliations
Review

HCV Proteins Modulate the Host Cell miRNA Expression Contributing to Hepatitis C Pathogenesis and Hepatocellular Carcinoma Development

Devis Pascut et al. Cancers (Basel). .

Abstract

Hepatitis C virus (HCV) genome encodes for one long polyprotein that is processed by cellular and viral proteases to generate 10 polypeptides. The viral structural proteins include the core protein, and the envelope glycoproteins E1 and E2, present at the surface of HCV particles. Non-structural (NS) proteins consist of NS1, NS2, NS3, NS4A, NS4B, NS5a, and NS5b and have a variable function in HCV RNA replication and particle assembly. Recent findings evidenced the capacity of HCV virus to modulate host cell factors to create a favorable environment for replication. Indeed, increasing evidence has indicated that the presence of HCV is significantly associated with aberrant miRNA expression in host cells, and HCV structural and non-structural proteins may be responsible for these alterations. In this review, we summarize the recent findings on the role of HCV structural and non-structural proteins in the modulation of host cell miRNAs, with a focus on the molecular mechanisms responsible for the cell re-programming involved in viral replication, immune system escape, as well as the oncogenic process. In this regard, structural and non-structural proteins have been shown to modulate the expression of several onco-miRNAs or tumor suppressor miRNAs.

Keywords: HCC; HCV; hepatitis C; miRNAs; microRNA; viral proteins.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Proteins encoded by the HCV genome. HCV viral genome encodes one long polyprotein that is co- and post-translationally processed into mature structural and non-structural proteins. The viral structural proteins (green) include the core protein and envelope glycoproteins E1 and E2; the viral non-structural proteins (orange) consist of NS1, NS2, NS3, NS4A, NS4B, NS5A, and NS5B proteins.
Figure 2
Figure 2
MiRNAs regulated by envelope and non-structural proteins in host cells. E2 proteins induce the release of exosomal miR-490 from mast cells and its internalization by hepatocytes reduced cell migration. NS3 proteins, by modulating miR-155, miR-21, and miR-122, determine inflammation, immune escape, and fibrosis. NS4B, through the modulation of miR-27a and b, affects the lipid metabolism. NS5A inhibits the expression of two oncosuppressor miRNAs, miR-503 and miR-181c.
Figure 3
Figure 3
List of miRNA participating in cancerogenesis. HCV proteins regulated several miRNAs that are involved in multiple oncogenic processes.
See this image and copyright information in PMC

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