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

被引:43
|
作者
Ninomiya, M. [1 ]
Kondo, Y. [1 ,2 ]
Kimura, O. [1 ]
Funayama, R. [3 ]
Nagashima, T. [3 ]
Kogure, T. [1 ]
Morosawa, T. [1 ]
Tanaka, Y. [4 ,5 ]
Nakayama, K. [3 ]
Shimosegawa, T. [1 ]
机构
[1] Tohoku Univ Hosp, Div Gastroenterol, 1-1 Seiryo, Sendai, Miyagi 9808574, Japan
[2] Sendai Kousei Hosp, Dept Hepatol, Sendai, Miyagi, Japan
[3] Tohoku Univ Med, Div Cell Proliferat, Sendai, Miyagi, Japan
[4] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi, Japan
[5] Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi, Japan
关键词
deep sequencing; hepatitis B virus; luciferase reporter assay; MicroRNAs; miR-125b-5p; IN-VITRO; MICRORNAS; MODULATION; MECHANISM; ABUNDANCE; GENES; RNAS;
D O I
10.1111/jvh.12522
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:330 / 339
页数:10
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