Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study
Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study
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microRNA 表达谱分析确定 miR-155 和 miR-155* 作为活动性结核病的潜在诊断标志物：初步研究
DOI：
10.1016/j.humimm.2011.10.003
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发表时间：
2012-01-01
期刊：
影响因子：
2.7
通讯作者：
Huang, Yuxian
中科院分区：
文献类型：
--
作者：
Wu, Jing;Lu, Chanyi;Huang, Yuxian
为了探讨microRNAs(MiRNAs)在活动性结核病(ATB)发生发展中的生物学行为和疾病相关性，我们研究了结核分枝杆菌(MTB)纯化蛋白衍生物(PPD)诱导的miRNAs的表达谱，以确定参与ATB发病机制的特异性miRNAs。首先用微阵列技术检测了PPD刺激下ATB患者和健康对照组(HC)外周血单个核细胞中miRNA的表达谱。然后，通过定量实时聚合酶链式反应(qRT-PCR)在更大的队列中验证显著反应的miRNAs。绘制受试者工作特征(ROC)曲线以评价所确定的PPD反应miRNAs的诊断价值。计算程序还预测了这些miRNAs的潜在靶点。在ATB组和HC组之间，866个人miRNAs中有14个在PPD刺激前后的表达水平比率至少相差1.8倍。定量逆转录聚合酶链式反应研究证实了基于微阵列的筛选结果，在pPD刺激下，miR-155在HC组和ATB组分别显示了1.4%和3.7%的倍数变化(p<；0.0001)；miR-155*在HC组和ATB组显示了1.9%和4.6%的倍数变化(p<；0.005)。在ROC图中，MIR-155和MIR-155*的曲线下面积分别为0.8972和0.7945。在ATB组和HC组中，这两个microRNAs的背景表达没有差异。MIR-155和miR-155*表现出结核特异性抗原的特异性表达，提示它们可以作为结核分枝杆菌特异性抗原攻击下的潜在诊断标记物。(C)2012年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版，版权所有。
To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p < 0.0001); miR-155* exhibited a fold change of 1.9 in the HC and 4.6 in the ATB group (p < 0.005). In ROC plots, the area under the curve was 0.8972 for miR-155 and 0.7945 for miR-155*. The background expression of these 2 microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.