The association of microRNA expression in peripheral blood lymphocytes and disease progression of chronic hepatitis C patients

碩士 === 中山醫學大學 === 醫學研究所 === 100 === Objective:Infection with the hepatitis C virus is one of the risk factors in the development of liver cancer. This aim of this study is to understand the effect of microRNA expression levels on hepatitis C development and treatment response, and to provide evidenc...

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Bibliographic Details
Main Authors: Wan-Ling, 謝宛玲
Other Authors: Ya-Wen Cheng
Format: Others
Language:zh-TW
Published: 2012
Online Access:http://ndltd.ncl.edu.tw/handle/46495556202021854265
Description
Summary:碩士 === 中山醫學大學 === 醫學研究所 === 100 === Objective:Infection with the hepatitis C virus is one of the risk factors in the development of liver cancer. This aim of this study is to understand the effect of microRNA expression levels on hepatitis C development and treatment response, and to provide evidence that the expression levels of microRNA can be used as biomarkers for the diagnosis and assessment of recurrence of hepatitis C. Materials and Methods:First, peripheral blood lymphocytes (PBLs) were collected from 10 hepatitis C patients and 10 health controls for microRNA profile analysis. Based on the resulting microarray data and published references, 7 candidate microRNAs were selected, and real-time RT-PCR was used to further confirm the microRNAs and target genes expression in patient’s PBLs. In addition, the down-stream genes Mcl-1 and Cyclin D1 were also analyzed through real-time RT-PCR. Results:In chronic hepatitis C patients’ PBLs, miR-16, miR-193b, miR-199a-3p, miR-222 , and miR-324-3p expression levels were increased and miR-122 expression was decreased, in comparison with the health control group. After IFN-alfa and Ribavirin treatment, only miR-222 expression levels were decreased, while miR-16, miR-122, miR-193b and miR-199a-3p expression were increased. In addition, the expression levels of miR-324-3p in HCV genotype-1 and non-SVR patients were increased, but were decreased in the expression levels of HCV genotype-non1 patients, when compared with non-treatment. Three to six months after the end of treatment, the expression of these microRNAs were increased. Further analysis of the downstream genes Mcl-1and cyclin D1 of these microRNA showed that mcl-1 was negatively correlated with miR-193b, miR-199a-3p, and miR-324-3p expression, while Cyclin D1 was only negatively correlated to miR-16 and miR-324-3p. Conclusion and Suggestions:This study did not find a direct correlation between microRNA expression and the effects of IFN-alfa and Ribavirin treatment in patients with hepatitis C, but miR-193b miR-199a-3p showed high specifics for hepatitis C diagnosis. It is suggested that changes in microRNA expression may correlate with immune regulation, but this requires further study.