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丙型肝炎病毒感染患者血清微小RNA表达谱失调及潜在生物标志物

Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients.

作者信息

Zhang Shaobo, Ouyang Xiaoxi, Jiang Xin, Gu Dayong, Lin Yulong, Kong S K, Xie Weidong

机构信息

1. Shenzhen Key Lab of Health Science and Technology, Division of Life Science & Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China ; 2. Zhu Jiang Hospital, Southern Medical University, Guangzhou 510282, China.

1. Shenzhen Key Lab of Health Science and Technology, Division of Life Science & Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China ; 3. Department of health inspection and quarantine, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Int J Med Sci. 2015 Jul 16;12(7):590-8. doi: 10.7150/ijms.11525. eCollection 2015.

Abstract

OBJECTIVES

Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection.

METHODS

Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR-134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection.

RESULTS

miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR-629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation.

CONCLUSION

HCV patients have a broad 'fingerprint' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation.

摘要

目的

循环微小RNA(miRNA)在病原体与宿主的相互作用中发挥关键作用。异常的miRNA表达谱可能具有病毒株的特定特征,并可作为筛查和诊断传染病的非侵入性生物标志物。在本研究中,我们旨在寻找丙型肝炎病毒(HCV)感染新的潜在miRNA生物标志物。

方法

使用miRNA PCR阵列分析10例HCV病毒血症患者和10名健康志愿者血清样本中广谱miRNA的表达水平。随后,通过qRT-PCR验证了39例患者血清中4种选定miRNA(miR-122、miR-134、miR-424-3p和miR-629-5p)与29名健康对照者血清中的差异表达。进行受试者操作特征(ROC)曲线分析以评估它们诊断HCV感染的潜力。

结果

miRNA PCR阵列分析显示,与健康对照相比,HCV患者血清中106种miRNA存在差异表达。血清hsa-miR-122、miR-134、miR-424-3p和miR-629-5p得到了很好的鉴定。ROC曲线显示,miR-122、miR-134、miR-424-3p和miR-629-5p能够以较好的敏感性和特异性区分HCV患者。此外,相关性分析表明血清miR-122表达与ALT/AST水平呈正相关。对这些miRNA靶蛋白的功能分析表明其参与病毒复制、炎症和细胞增殖。

结论

与健康对照相比,HCV患者血清miRNA失调,具有广泛的“指纹”特征。其中,血清hsa-miR-122、miR-134、miR-424-3p和miR-629-5p被确定为HCV感染血清miRNA谱有前景的指示因子。特别是,miR-122可能是HCV早期病理过程的血清生物标志物之一。然而,更多的miRNA生物标志物以及这些miRNA的生物学功能需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6c6/4532963/f887eb19a73e/ijmsv12p0590g001.jpg

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