Yonsei Med J.  2018 Jun;59(4):511-518. 10.3349/ymj.2018.59.4.511.

miR-215 Enhances HCV Replication by Targeting TRIM22 and Inactivating NF-κB Signaling

Affiliations
  • 1Department of Infectious Disease, Huaihe Hospital of Henan University, Kaifeng, China. hezhenshenccn@163.com

Abstract

PURPOSE
Hepatitis C virus (HCV) infection is a major cause of liver disease. Several miRNAs have been found to be associated with HCV infection. This study aimed to investigate the functional roles and possible molecular mechanisms of miR-215 in HCV replication.
MATERIALS AND METHODS
The expression levels of miR-215 and TRIM22 were detected by quantitative real-time PCR (qRT-PCR) and western blot analysis in Con1b subgenomic genotype 1b HCV replicon cells (Con1b cells) and JFH1 full genome infecting Huh7.5.1 cells (Huh7.5.1 cells). HCV RNA levels were measured by qRT-PCR. The protein levels of NS3, NS5A, p65 subunit of NF-κB (p65), and phosphorylated p65 (p-p65) were determined by western blot analysis. The relationship between miR-215 and TRIM22 were explored by target prediction and luciferase reporter analysis.
RESULTS
miR-215 overexpression enhanced HCV replication in Con1b cells, while miR-215 knockdown suppressed HCV replication in Huh7.5.1 cells. TRIM22 was confirmed to be a direct target of miR-215. TRIM22 upregulation resulted in a decline in HCV replication, while TRIM22 inhibition led to enhancement of HCV replication. Additionally, exogenous expression of TRIM22 reversed the facilitating effect of miR-215 on HCV replication, while TRIM22 downregulation counteracted the inhibitory effect of miR-215 knockdown on HCV replication. Furthermore, miR-215 targeted TRIM22 to block the NF-κB pathway, and exerted a positively regulatory role on HCV replication.
CONCLUSION
miR-215 facilitated HCV replication via inactivation of the NF-κB pathway by inhibiting TRIM22, providing a novel potential target for HCV infection.

Keyword

miR-215; tripartite motif 22; hepatitis C virus; NF-κB

MeSH Terms

Blotting, Western
Down-Regulation
Genome
Genotype
Hepacivirus
Liver Diseases
Luciferases
MicroRNAs
Real-Time Polymerase Chain Reaction
Replicon
RNA
Up-Regulation
Luciferases
MicroRNAs
RNA
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