中重度哮喘和轻度哮喘差异表达microRNA及生物信息学分析  

Microarray screening and bioinformatics analysis of differentially expressed microRNAs in moderate-severe asthma compared to mild asthma

作　　者：罗雅妮 熊轶[1] LUO Ya-ni;XIONG Yi(Biomedical Research Institute,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen,Guangdong Province 518036 China)

机构地区：[1]深圳北京大学香港科技大学医学中心生物医学研究所,广东深圳518036

出　　处：《解剖学研究》2023年第2期143-148,152,共7页Anatomy Research

基　　金：广东省自然科学基金项目(2020A1515011040)。

摘　　要：目的 探讨中重度哮喘生物标志物和致病机制,为更有效的中重度哮喘治疗和控制提供线索。方法 采用microRNA芯片检测中重度哮喘患者与轻度哮喘患者血清中的差异表达microRNA。通过miRanda,TargetScan,RNAhybrid和miRTarbase数据库对microRNA的靶基因进行预测,并使用GO功能聚类分析和KEGG信号通路富集分析对microRNA的靶基因进行功能解析。使用qRT-PCR检验慢性哮喘小鼠肺组织中microRNA的含量。结果 与轻度哮喘患者相比,miR-4746-3p、miR-6798-5p和miR-762等在中重度哮喘患者血清中上调,而miR-26a-5p、miR-377-3p和miR-410-3p等下调。与轻度哮喘相比,慢性炎症调控、脂质吸收、储存、分解代谢功能及PI3K-Akt信号通路、Wnt信号通路、TOR复合体等细胞增殖相关通路在中重度哮喘中显著富集。此外,慢性哮喘模型鼠呈现出与重度哮喘患者类似的病理表型如炎性细胞浸润与气道重塑,且miR-377-3p和miR-410-3p在慢性哮喘小鼠肺组织中也显著下调。结论 我们的研究提供了中重度哮喘可能的非侵入性风险生物标志物。为中重度哮喘患者的炎症及气道细胞成分如平滑肌细胞,黏液腺细胞,血管内皮细胞增生肥大引起的气道重塑提供了可能的分子机制和信号通路,这些发现可为更有效的重度哮喘治疗和控制提供理论基础。Objective Severe asthma has imposed a heavy burden on patients and medical resources.Identifying its biomarkers and pathogenesis is urgently needed to provide clues for the effective treatment and management of severe asthma.Methods The microRNA array was used to detect differentially expressed microRNAs in the serum of patients with moderate-severe asthma compared to patients with mild asthma.Target genes of microRNAs were predicted by miRanda,TargetScan,RNAhybrid and miRTarbase databases.The functional annotation of target genes of microRNAs was analyzed by GO functional enrichment analysis and KECG Pathway enrichment analysis.The expression of microRNAs in lung of mice with chronic asthma was detected by qRT-PCR.Results Compared to patients with mild asthma,miR-4465,miR-6798-5p and miR-762 etc were up-regulated in the serum of patients with moderate-severe asthma,while miR-26a-5p,miR-377-3p and miR-410-3p etc were down-regulated.Bioinformatics analysis results show that the target genes involved in the regulation of chronic inflammatory response,lipid absorption,storage,catabolic process and cell proliferation-related pathway including PI3K-Akt signaling pathway Wnt signalling pathway and TOR complex are enriched in moderate-severe asthma.In addition,chronic asthma mice represent pathological phenotypes similar to severe asthma patients,such as inflammation and airway remodeling.miR-377-3p and miR-410-3p were also significantly down-regulated in lung tissue of mice with chronic asthma.Conclusions The differentially expressed microRNAs in the serum of patients may be used as non-invasive biomarkers to distinguish moderate-severe asthma from mild asthma patients.Our findings also provide possible molecular mechanisms underlying the inflammation and airway remodeling.These findings may provide knowledge for the effective treatment and management of severe asthma.

关 键 词：哮喘 microRNA芯片 气道重塑 气道炎症 

分 类 号：R562.25[医药卫生—呼吸系统] Q811.4[医药卫生—内科学]