Circulating microRNAs and association with methacholine PC20 in the Childhood Asthma Management Program (CAMP) cohort.
Circulating microRNAs and association with methacholine PC20 in the Childhood Asthma Management Program (CAMP) cohort.
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DOI：
10.1371/journal.pone.0180329
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发表时间：
2017
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：
Davis JS;Sun M;Kho AT;Moore KG;Sylvia JM;Weiss ST;Lu Q;Tantisira KG
循环microRNA（microRNA，miRNA）是一种很有前途的人类疾病生物标志物。我们的研究假设循环中的miRNA将揭示与气道高反应性（AHR）相关的候选生物标志物，并为哮喘表观遗传影响提供生物学见解。在儿童哮喘管理项目中随机抽取的160名儿童的血清样本使用TaqMan miRNA阵列集进行分析。评估分离的miRNA与乙酰甲胆碱PC 20的关联。进行了网络和通路分析。在人气道平滑肌细胞（HASMs）中进行两种重要miRNA的功能验证。在155种检测良好的循环miRNA中，8种与PC 20显著相关，其中与miR-296- 5 p的相关性最强。通路分析揭示miR-16- 5 p作为网络枢纽，并且通过KEGG分析涉及与FoxO和Hippo信号通路中的基因相互作用的多种miRNA。两种miRNA在HASM中的功能验证显示了对细胞生长和直径的影响。基线时循环miRNA表达减少与PC 20增加相关。这些miRNA提供了对哮喘严重程度的生物学见解，并可作为哮喘严重程度的生物标志物。miR-16- 5 p和-30d-5p调节气道平滑肌表型，这些表型与哮喘发病机制密切相关，支持与这些发现的机制联系。功能性ASM表型可能与AHR直接相关。
Circulating microRNAs (miRNA) are promising biomarkers for human diseases. Our study hypothesizes that circulating miRNA would reveal candidate biomarkers related to airway hyperresponsiveness (AHR) and provide biologic insights into asthma epigenetic influences. Serum samples obtained at randomization for 160 children in the Childhood Asthma Management Program were profiled using a TaqMan miRNA array set. The association of the isolated miRNA with methacholine PC20 was assessed. Network and pathway analyses were performed. Functional validation of two significant miRNAs was performed in human airway smooth muscle cells (HASMs). Of 155 well-detected circulating miRNAs, eight were significantly associated with PC20 with the strongest association with miR-296-5p. Pathway analysis revealed miR-16-5p as a network hub, and involvement of multiple miRNAs interacting with genes in the FoxO and Hippo signaling pathways by KEGG analysis. Functional validation of two miRNA in HASM showed effects on cell growth and diameter. Reduced circulatory miRNA expression at baseline is associated with an increase in PC20. These miRNA provide biologic insights into, and may serve as biomarkers of, asthma severity. miR-16-5p and -30d-5p regulate airway smooth muscle phenotypes critically involved in asthma pathogenesis, supporting a mechanistic link to these findings. Functional ASM phenotypes may be directly relevant to AHR.
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影响因子：
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作者：
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通讯作者：
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