miRNA分析显示,儿童哮喘、肥胖及其共病具有共同特征

miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity.

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摘要(中文译文)

儿童肥胖是已知的哮喘危险因素,可导致疾病严重程度增加和皮质类固醇反应性降低。然而,这种共病背后的分子机制仍不清楚。我们采用横断面设计,旨在识别与儿童哮喘-肥胖共病相关的microRNA(miRNA)特征,以揭示潜在的共同分子驱动因素。采集了四组儿童的全血样本:正常体重伴哮喘组(NW-A,n=11)、超重/肥胖伴哮喘组(OO-A,n=10)、超重/肥胖不伴哮喘组(OO,n=10)以及正常体重不伴哮喘组(NW,n=12)。使用NanoString nCounter平台评估循环miRNA谱。使用Enrichr及其他生物信息学工具进行差异表达和通路富集分析。通过Pearson相关分析和多元回归分析评估与临床及细胞因子数据的相关性。四组之间的miRNA表达谱存在显著差异。五种miRNA(miR-423-3p、-92a-3p、-4536-5p、-197-3p、-891a-5p)在单纯哮喘、单纯肥胖及哮喘-肥胖共病中一致上调,两种miRNA(miR-144-3p、-641)一致下调。对OO-A相关miRNA的靶基因分析显示其参与IL-4、IL-13和PIP3/AKT信号通路,以及与先天免疫和代谢相关的通路。在OO-A组中,miRNA失调与中性粒细胞升高、促炎细胞因子升高及肺功能降低相关。在这项探索性研究中,我们识别了哮喘-肥胖共病中共有的循环miRNA特征。这些miRNA可能作为生物标志物和潜在治疗靶点,用于肥胖儿童哮喘的分层和管理,尚需纵向研究验证。

Abstract

Childhood obesity is a known risk factor for asthma and contributes to increased disease severity and reduced corticosteroid responsiveness. However, the molecular mechanisms underlying this comorbidity remain unclear. Using a cross-sectional design, we aimed to identify microRNA (miRNA) signatures associated with asthma-obesity comorbidity in children to shed light on potential shared molecular drivers. Whole blood samples were collected from four pediatric groups: normal weight with asthma (NW-A, n = 11), overweight/obesity with asthma (OO-A, n = 10), overweight/obesity without asthma (OO, n = 10), and normal weight without asthma (NW, n = 12). Circulating miRNA profiles were assessed using the NanoString nCounter platform. Differential expression and pathway enrichment analyses were performed using Enrichr and other bioinformatic tools. Correlation with clinical and cytokine data was assessed by Pearson's correlation and multiple regression analyses. miRNA expression profiles differed markedly across the four groups. Five miRNAs (miR- 423-3p, -92a-3p, -4536-5p, -197-3p, -891a-5p) were consistently upregulated, and two (miR-144-3p, -641) were downregulated across asthma alone, obesity alone, and asthma-obesity comorbidity. Target gene analysis of OO-A-associated miRNAs highlighted involvement in IL-4, IL-13, and PIP3/AKT signaling, as well as pathways linked to innate immunity and metabolism. In OO-A, miRNA dysregulation was correlated with elevated neutrophils, pro-inflammatory cytokines, and reduced lung function. In this exploratory study, we identified a shared circulating miRNA signature in asthma-obesity comorbidity. These miRNAs may serve as biomarkers and potential therapeutic targets for stratifying and managing asthma in children with obesity, pending validation in longitudinal studies.

如何引用

AMA

Harshita Shailesh, Mohamed Nadhir Djekidel, Safa Noor, Lena Hayati, Stefan Worgall, Souhaila Al Khodor, et al. miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1792996.

APA

Harshita Shailesh, Mohamed Nadhir Djekidel, Safa Noor, Lena Hayati, Stefan Worgall, Souhaila Al Khodor, et al (2026). miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1792996

GB/T 7714

Harshita Shailesh, Mohamed Nadhir Djekidel, Safa Noor, Lena Hayati, Stefan Worgall, Souhaila Al Khodor, et al. miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1792996.

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