循环MicroRNAs：与哮喘肺功能的关系
2016/08/22
摘要
背景：MicroRNA是关键的转录和网络调节因子，此前研究表明其与哮喘易感性相关。然而，他们与哮喘的严重程度的相互关系并没有被描述清楚。
目标：我们假设循环microRNAs可作为哮喘患者肺功能变化的生物标志物。
方法：我们从儿童哮喘管理项目中随机抽取160名参与者，从中提取血清样品并分离microRNA。使用含754 个microRNA引物的TaqMan microRNA芯片，我们测试已知存在的哮喘相关microRNAs，并通过测定FEV1/FVC、FEV1%和FVC%来评估个体microRNAs与肺功能之间的关系。我们还进一步检测了与性别差异以及肺发育相关的FEV1/FVC microRNAs亚群。
结果：在108种明确检测到的循环microRNAs中，74种（68.5%）前期被证明与哮喘易感性有关。我们发现分别有22种（20.3%），4种（3.7%）和8种（7.4%）的microRNAs分别与FEV1/FVC，FEV1%和FVC %相关。其中8种（22种中）FEV1／FVC、3种（4种中）FEV1 %和1种（8种中）FVC%的microRNAs存在功能验证的靶基因，全基因组关联分析显示，这些靶基因与哮喘和FEV1的变化有关。在性别相关性分析中，22种 FEV1/FVC microRNAs中，有9种（40.9%）与男孩FEV1/FVC相关（3种microRNAs仅与女孩的 FEV1/FVC相关），7种（31.8%）与胎肺发育有关，3种（13.6%）与上述两项均相关。本体论分析揭示了哮喘信号通路的补充，包括PPAR信号，G蛋白偶联的信号，肌动蛋白和肌球蛋白的结合，以及呼吸系统的发育。
结论：循环microRNAs反应了哮喘生物学特征，与哮喘患者肺功能差异有关。他们可能成为哮喘严重程度的生物标志物之一。
（苏欣 审校）
PLoS One. 2016 Jun 30;11(6):e0157998. doi: 10.1371/journal.pone.0157998. eCollection 2016.
Circulating MicroRNAs: Association with Lung Function in Asthma.
Kho AT1, Sharma S2, Davis JS3,4, Spina J3, Howard D5, McEnroy K3, Moore K3, Sylvia J3, Qiu W3, Weiss ST3,6, Tantisira KG3,7.
Author information
Abstract
BACKGROUND:MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated.
OBJECTIVE:We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients.
METHODS: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.
RESULTS: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.
CONCLUSIONS:Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.
PLoS One. 2016 Jun 30;11(6):e0157998. doi: 10.1371/journal.pone.0157998. eCollection 2016.
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