Circulating MicroRNAs: Association with Lung Function in Asthma.
Circulating MicroRNAs: Association with Lung Function in Asthma.
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DOI：
10.1371/journal.pone.0157998
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tantisira KG
中科院分区：
文献类型：
--
作者：
Kho AT;Sharma S;Davis JS;Spina J;Howard D;McEnroy K;Moore K;Sylvia J;Qiu W;Weiss ST;Tantisira KG
microrna是先前与哮喘易感性相关的关键转录和网络调节因子。然而，它们在哮喘严重程度中的作用尚未明确。我们假设循环microrna可以作为哮喘患者肺功能变化的生物标志物。我们从随机抽取的160名儿童哮喘管理项目参与者的血清样本中分离出microrna。使用TaqMan microRNA阵列，包含754个microRNA引物，我们检测了已知哮喘microRNA的存在，并评估了单个microRNA与肺功能的关联，测量FEV1/FVC， FEV1%和FVC%。我们进一步测试了FEV1/FVC microrna亚群的性别特异性和肺发育相关性。在108个检测良好的循环microrna中，74个（68.5%）先前与哮喘易感性有关。我们发现22个（20.3%）、4个（3.7%）和8个（7.4%）microrna分别与FEV1/FVC、FEV1%和FVC%相关。8（22）个FEV1/FVC， 3(4)个FEV1%和1(8)个FVC%的microrna具有功能验证的靶基因，这些靶基因已通过全基因组关联研究与哮喘和FEV1变化联系起来。在22个FEV1/FVC microrna中，在性别分层分析中，9个（40.9%）仍然与单独男孩的FEV1/FVC相关（相比之下，单独女孩的FEV1/FVC microrna为3个），7个（31.8%）与胎儿肺发育相关，3个（13.6%）与两者相关。本体论分析显示哮喘不可或缺的通路丰富，包括PPAR信号、g蛋白偶联信号、肌动蛋白和肌球蛋白结合以及呼吸系统发育。循环microrna反映哮喘生物学，并与哮喘患者肺功能差异相关。它们可能代表哮喘严重程度的生物标志物。
MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated. We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients. We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations. Of the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development. Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.