Issue 15, 2018, Issue in Progress

MiR-29c inhibits HCV replication via activation of type I IFN response by targeting STAT3 in JFH-1-infected Huh7 cells

Abstract

Background: MiR-29c, a member of the miR-29 family, has been recognized to play an important role in hepatitis C virus (HCV) infection. However, the underlying molecular mechanism of miR-29c involved in HCV replication is not fully understood. Methods: RT-qPCR assay was used to detect the expression pattern of miR-29c and signal transducer and activator of transcription 3 (STAT3) mRNA in JFH-1-infected Huh7 cells. HCV replication was evaluated by the expression of HCV RNA, non-structural protein 5A (NS5A) and non-structural protein 3 (NS3). Dual-Luciferase Reporter assay was applied to search for the candidate target mRNAs of miR-29c. Western blot assay was performed to detect the protein level of double-stranded RNA-dependent protein kinase R (PKR), (2′-5′)-oligoadenylate synthetase (OAS) and interferon regulatory transcription factor 1 (IRF1). Results: miR-29c expression was down-regulated, and STAT3 mRNA and protein expressions were up-regulated in JFH-1-infected Huh7 cells. MiR-29c overexpression or STAT3 knockdown repressed HCV replication, while miR-29c depletion or STAT3 upregulation promoted HCV replication. Additionally, STAT3 was a direct target of miR-29c, and miR-29c suppressed STAT3 protein expression in Huh7 cells. Moreover, STAT3 overexpression reversed miR-29c-mediated suppression on HCV replication. Furthermore, the anti-miR-29c-mediated inhibitory effect on type I IFN response was abated following STAT3 knockdown. Conclusions: miR-29c might repress HCV infection via promoting type I IFN response by targeting STAT3 in JFH-1-infected Huh7 cells, offering a promising avenue for HCV treatment.

Graphical abstract: MiR-29c inhibits HCV replication via activation of type I IFN response by targeting STAT3 in JFH-1-infected Huh7 cells

Article information

Article type
Paper
Submitted
27 Nov 2017
Accepted
13 Feb 2018
First published
20 Feb 2018
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2018,8, 8164-8172

MiR-29c inhibits HCV replication via activation of type I IFN response by targeting STAT3 in JFH-1-infected Huh7 cells

Y. Wang and Y. Li, RSC Adv., 2018, 8, 8164 DOI: 10.1039/C7RA12815K

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