Plasma microRNA profiling predicts HIV-associated neurocognitive disorder
Plasma microRNA profiling predicts HIV-associated neurocognitive disorder
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DOI：
10.1097/qad.0000000000001160
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发表时间：
2016-08-24
期刊：
影响因子：
3.8
通讯作者：
Power, Christopher
中科院分区：
文献类型：
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作者：
Asahchop, Eugene L.;Akinwumi, Segun M.;Power, Christopher
目的：HIV相关的神经认知障碍（HAND）是HIV感染患者中常见的神经系统疾病，尽管联合抗逆转录病毒治疗可用。宿主编码的微小RNA（miRNA）调节宿主和病毒基因表达，从而促进HAND发病机制，并且还可以充当疾病生物标志物。在此，血浆miRNA谱在HIV/AIDS患者与HAND.Methods：发现和验证队列包括HIV/AIDS患者进行了研究，其中包括患者和没有HAND（非HAND）。通过阵列杂交测量血浆miRNA水平，并通过定量实时逆转录酶PCR（qRT-PCR）验证。结果：表达分析鉴定了发现队列（HAND，n = 22;非HAND，n = 25）中的9种miRNA，与非HAND组相比，HAND组中的水平增加（>=两倍）（P < 0.05）。在验证队列（HAND，n = 12;非HAND，n = 12）中，在HAND组中观察到三种miRNA（miR-3665、miR-4516和miR-4707- 5 p）的上调（>=两倍），其在发现队列的HAND患者中也增加，随后通过qRT-PCR验证。三种miRNAs的受试者工作特征曲线分析也指出了HAND的诊断（曲线下面积，0.87，P < 0.005）。生物信息学工具预测，所有三个miRNA的靶向序列的基因牵连在神经发育，细胞死亡，炎症，细胞信号传导和细胞因子functions.Conclusion：差异表达的血浆衍生的miRNA检测在HIV/AIDS患者的手，保守在不同的患者队列和实验室方法。血浆来源的miRNAs可能代表HAND的生物标志物，也为疾病机制提供了见解。版权所有（C）2016威科医疗集团All rights reserved.
Objective: HIV-associated neurocognitive disorder (HAND) is a common neurological disorder among HIV-infected patients despite the availability of combination antiretroviral therapy. Host-encoded microRNAs (miRNA) regulate both host and viral gene expression contributing to HAND pathogenesis and can also serve as disease biomarkers. Herein, plasma miRNA profiles were investigated in HIV/AIDS patients with HAND.Methods: Discovery and Validation Cohorts comprising HIV/AIDS patients were studied that included patients with and without HAND (non-HAND). Plasma miRNA levels were measured by array hybridization and verified by quantitative real-time reverse transcriptase PCR (qRT-PCR). Multiple bioinformatic and biostatistical analyses were applied to the data from each cohort.Results: Expression analyses identified nine miRNAs in the Discovery Cohort (HAND, n = 22; non-HAND, n = 25) with increased levels (>= two-fold) in the HAND group compared with the non-HAND group (P < 0.05). In the Validation Cohort (HAND, n = 12; non-HAND, n = 12) upregulation (>= two-fold) of three miRNAs (miR-3665, miR-4516 and miR-4707-5p) was observed in the HAND group that were also increased in the Discovery Cohort's HAND patients, which were verified subsequently by qRT-PCR. Receiver-operating characteristic curve analyses for the three miRNAs also pointed to the diagnosis of HAND (area under curve, 0.87, P < 0.005). Bioinformatics tools predicted that all three miRNAs targeted sequences of genes implicated in neural development, cell death, inflammation, cell signalling and cytokine functions.Conclusion: Differentially expressed plasma-derived miRNAs were detected in HIV/AIDS patients with HAND that were conserved across different patient cohorts and laboratory methods. Plasma-derived miRNAs might represent biomarkers for HAND and also provide insights into disease mechanisms. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.