MicroRNA profile before and after antiviral therapy in liver transplant recipients for hepatitis C virus cirrhosis
MicroRNA profile before and after antiviral therapy in liver transplant recipients for hepatitis C virus cirrhosis
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DOI：
10.1111/jgh.12362
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Kiss, Andras
中科院分区：
文献类型：
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作者：
Gelley, Fanni;Zadori, Gergely;Kiss, Andras
背景与目的丙型肝炎病毒（HCV）复发的治疗是肝移植术后面临的主要挑战。HCV受体（即claudin-1、occludin、tetraspanin CD81、清道夫受体B1型）的显著失调表达最近在HCV感染期间被发现。这可能促进肝细胞进入和HCV的再感染。MicroRNAs （miRs）在基因表达调控中发挥重要作用。我们的目的是表征成人肝移植受者中与HCV感染和抗病毒治疗相关的miR表达谱，特别强调预测靶向HCV受体的miR。方法选取28例成人肝移植受者为研究对象。在HCV复发时和抗病毒治疗结束时进行配对活检。使用靶标预测软件选择HCV受体的MiRs。通过逆转录-定量聚合酶链反应检测miR-21、miR-23a、miR-34a、miR-96、miR-99a*、miR-122、miR-125b、miR-181a-2*、miR-194、miR-195、miR-217、miR-221、miR-224的表达水平。结果HCV复发组织中mir -99a*和miR-224表达升高，miR-21和miR-194表达降低。与HCV复发样本相比，抗病毒治疗后的样本中miR-221、miR-224和miR-217的表达增加。复发时HCV滴度高与miR-122水平升高相关。结论HCV复发和抗病毒治疗后的样本显示出不同的HCV相关miR表达谱，这些mirna可能靶向HCV受体mrna。特别是，miR-194和miR-21可能参与HCV感染和抗病毒治疗过程中HCV受体蛋白表达的调控。
Background and AimManagement of hepatitis C virus (HCV) recurrence is a major challenge after liver transplantation. Significant dysregulated expression of HCV receptors (i.e. claudin-1, occludin, tetraspanin CD81, scavenger receptor type B1) has been shown recently during HCV infection. This might facilitate hepatocytic entry and reinfection of HCV. MicroRNAs (miRs) play role in the regulation of gene expression. We aimed to characterize miR expression profiles related to HCV infection and antiviral therapy in adult liver transplant recipients, with special emphasis on miRs predicted to target HCV receptors.MethodsTwenty-eight adult liver transplant recipients were enrolled in the study. Paired biopsies were obtained at the time of HCV recurrence and at the end of antiviral treatment. MiRs for HCV receptors were selected using target prediction software. Expression levels of miR-21, miR-23a miR-34a, miR-96, miR-99a*, miR-122, miR-125b, miR-181a-2*, miR-194, miR-195, miR-217, miR-221, and miR-224 were determined by reverse transcription-quantitative polymerase chain reaction.ResultsmiR-99a* and miR-224 expressions were increased in HCV recurrence samples, while miR-21 and miR-194 were decreased in comparison to normal liver tissue. Increased expressions of miR-221, miR-224, and miR-217 were observed in samples taken after antiviral therapy when compared with HCV recurrence samples. High HCV titer at recurrence was associated with higher level of miR-122.ConclusionsSamples at recurrence of HCV and after antiviral therapy revealed distinct HCV-related miR expression profiles, with significant dysregulation of those miRNAs potentially targeting mRNAs of HCV receptors. In particular, miR-194 and miR-21 might be involved in the regulation of HCV receptor proteins' expression during HCV infection and antiviral therapy.