Up-regulation of circulating miR-20a is correlated with hepatitis C virus-mediated liver disease progression.
Up-regulation of circulating miR-20a is correlated with hepatitis C virus-mediated liver disease progression.
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DOI：
10.1002/hep.26296
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发表时间：
2013-09
期刊：
影响因子：
13.5
通讯作者：
Ray, Ratna B.
中科院分区：
文献类型：
--
作者：
Shrivastava, Shubham;Petrone, Jessica;Steele, Robert;Lauer, Georg M.;Di Bisceglie, Adrian M.;Ray, Ratna B.
慢性丙型肝炎病毒（HCV）感染是美国肝纤维化和肝移植的主要原因之一。血液中循环的microRNA （miRNA）正成为病理状况的生物标志物。在本研究中，我们采用了一种系统的筛选方法，以确定HCV感染患者血浆/血清中不同阶段肝脏组织学疾病严重程度的上调mirna。我们首先筛选HCV感染纤维化患者的血清样本，并使用血清miRNA阵列分析与健康志愿者的血清进行比较，并鉴定出一组被调节的miRNA。随后的研究表明，与健康志愿者或非HCV相关肝病患者相比，HCV感染纤维化患者血清中的miR-20a和miR-92a水平显著上调。我们还观察到急性和慢性HCV感染患者的血浆miR-20a和miR-92a与健康志愿者相比有所增加。然而，这些mirna的血浆/血清水平与HCV病毒载量之间没有相关性。接下来，我们调查了HCV感染患者的纵向血浆样本。我们的研究结果表明，miR-20a和miR-92a在从急性到慢性感染的HCV感染患者中保持不变。另一方面，miR-92a的表达在急性到急性个体中降低。这些数据提供了证据，表明血浆/血清miR-20a和miR-92a水平有潜力作为HCV感染早期检测的敏感和具有成本效益的生物标志物。循环miR-20a可能作为HCV介导纤维化的潜在预测性生物标志物。
Chronic hepatitis C Virus (HCV) infection is one of the major causes of liver fibrosis and liver transplantation in the United States. Circulating microRNA (miRNA) in the blood are emerging as biomarkers for pathological conditions. In the present study, we performed a systematic screening approach to identify upregulated miRNAs in the plasma/serum of HCV infected patients with different stages of hepatic histological disease severity. We initially screened serum samples of HCV infected patients with fibrosis and compared with sera of healthy volunteers using serum miRNA array profiling, and identified a group of modulated miRNAs. Subsequent study demonstrated that miR-20a and miR-92a in HCV infected fibrosis patients sera were significantly upregulated when compared with that of healthy volunteers or non-HCV associated liver disease. We have also observed an increase of plasma miR-20a and miR-92a in acute and chronic HCV infected patients as compared to that of healthy volunteers. However, there was no correlation between the plasma/serum levels of any of these miRNAs with HCV viral loads. We next investigated longitudinal plasma samples from HCV infected patients. Our results suggested that miR-20a and miR-92a remained unaltered in HCV infected patients who progressed from acute to chronic infection. On the other hand, miR-92a expression was reduced in acute to resolved individuals. These data provide evidence that plasma/serum levels of miR-20a and miR-92a have potential as sensitive and cost effective biomarkers for early detection of HCV infection. The circulating miR-20a may serve as a potential for predictive biomarker in HCV mediated fibrosis.
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