title: The expression of miR-125b-5p is increased in the serum of patients with chronic hepatitis B infection and inhibits the detection of hepatitis B virus surface antigen.
abstract: MicroRNAs were first discovered as small endogenous RNA molecules and some viruses have been reported to interact with host miRNAs. By investigating miRNA expression in serum derived from HBV-infected patients, we have clarified the relationship between miRNA expression and chronic HBV infection. Additionally, we demonstrate the use of miRNAs as both novel biomarkers and new therapies against HBV. We included the sera of 20 patients with chronic HBV infection, sera of 20 patients with HCV infection and sera of 10 healthy controls in this study. The miRNA libraries were sequenced using a 32-mer single end sequence. The validation study of circulating miRNA in serum was conducted by qRT-PCR. The HBV genomic regions of genotype B and genotype C that were speculated to be targeted by miRNA were constructed using complementary oligonucleotides in the vectors. Reporter assays were performed 48 h after transfection. The expression levels of 21 miRNAs were found to be differentially expressed in the three groups. 10 miRNAs (hsa-miR-100-5p, miR-125b-5p, miR-193b-3p, miR-194-3p, miR-30a-3p, miR-30c-2-3p, miR-3591-5p, miR-4709-3p, miR-574-3p and miR-99a-5p) were found to be upregulated in CH-B by deep sequence analysis. The computer analysis showed that two regions of HBsAg are potential targets of miR-125b-5p and miR-30c-2-3p and that these miRNAs may downregulate the expression of HBV-S. The HBV genotype C segment speculated to be targeted by hsa-miR-125b-5p significantly decreased the expression of the reporter. This study indicated that expression of miR-125b-5p was related to the etiology of chronic hepatitis B infection and regulated the expression of HBsAg.
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ninomiya
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan.|Department of Hepatology, Sendai Kousei Hospital, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Kimura
authors.affiliation: Division of Cell Proliferation, Tohoku University of Medicine, Sendai, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Division of Cell Proliferation, Tohoku University of Medicine, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kogure
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Morosawa
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Division of Cell Proliferation, Tohoku University of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D044967:Serum / Q000821:virology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: MicroRNAs; deep sequencing; hepatitis B virus; luciferase reporter assay; miR-125b-5p