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miR-122 decreases HCV entry into hepatocytes through binding to the 3' UTR of OCLN mRNA.
MedLine Citation:
PMID:  25302477     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Analysis in silico suggests that occludin (OCLN), a key receptor for HCV entry into hepatocytes, is a candidate target of miR-122; the most abundant hepatic micro RNA. We aimed to determine if miR-122 can decrease HCV entry through binding to the 3' UTR of OCLN mRNA.
DESIGN: Huh 7.5 cells were co-transfected with luciferase construct containing 3' UTR of OCLN (pLuc-OCLN) and with selected miRNAs (0-50 nM) and luciferase activity was measured. Huh7.5 cells were also infected by viral particles containing lenti-miR122 genome or control virus. After 48 h the cells were infected with HCV pseudo-particles (HCVpp) and VSV pseudo-particles (VSVpp). After 72 h, luciferase activity was measured and HCVpp activity was normalized to VSVpp activity.
RESULTS: MiR-122 binds to the 3'-UTR of OCLN and down-regulates its expression; co-transfection of miR-122 mimic with pLuc-OCLN resulted in a significant decrease in luciferase activity [by 55% (P<0.01)], while a non-specific miRNA and a mutant miR-122 did not have any effect. miR-122 mimic significantly down-regulated (by 80%) OCLN protein in Huh7.5 cells. Accordingly, patients with chronic hepatitis C and higher levels of hepatic miR-122 have lower hepatic expression of OCLN. Immuno-fluorescence imaging showed a decrease in co-localization of OCLN and CLDN following miR-122 over-expression in HCV infected cells. Huh7.5 cells transiently expressing Lenti-miR122 system showed 42% (P<0.01) decrease in HCV entry.
CONCLUSION: This study uncovers a novel anti-viral effect of miR-122 on human liver cells and shows that over-expression of miR-122 can decrease HCV entry into hepatocytes through down-regulation of OCLN. This article is protected by copyright. All rights reserved.
Authors:
Hossein Sendi; Marjan Mehrab-Mohseni; David M Foureau; Sriparna Ghosh; Tracy L Walling; Nury Steuerwald; Philippe J Zamor; Keith J Kapln; Carl Jacobs; William A Ahrens; Mark W Russo; Mark G Clemens; Laura W Schrum; Herbert L Bonkovsky
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-10
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  -     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-10     Completed Date:  -     Revised Date:  2014-10-11    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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