Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease.

Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease.
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慢性阻塞性肺疾病患者外周血单个核细胞microRNA和mRNA调控的生物信息学分析

DOI:
10.1186/s12931-016-0486-5
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发表时间:
2017-01-05
影响因子:
5.8
通讯作者:
Chang Y
Chang Y
中科院分区:
医学2区
文献类型:
--
作者:
Dang X;Qu X;Wang W;Liao C;Li Y;Zhang X;Xu D;Baglole CJ;Shang D;Chang Y

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研究背景慢性阻塞性肺疾病(COPD)是一种进行性、不可逆的慢性炎症性疾病,以单核细胞、淋巴细胞和中性粒细胞募集增加为特征。正因为如此,以及外周血核细胞(PBMC)评估的便利性,PBMC的miRNA谱近年来对于各种疾病引起了越来越多的关注。因此,我们分析了miRNA和mRNA谱,以了解他们的调节网络之间的COPD受试者与吸烟者没有气流limited.MethodsmiRNA和mRNA谱PBMCs从合并的17吸烟者和14 COPD受试者进行了高通量芯片检测。通过q-PCR验证失调的miRNA的表达。结果与吸烟者相比,COPD患者中有8种miRNA表达上调,3种miRNA表达下调,其中miR-24- 3 p、miR-93- 5 p、miR-320 a和miR-320 b表达上调,miR-1273 g-3 p表达下调。生物信息学分析表明,NOD和TLR是miRNA与mRNA调控网络中最丰富的途径。miR-24- 3 p可调节IL-18、IL-1β、TNF、CCL 3和CCL 4,miR-93- 5 p可调节IκBα。结论COPD患者PBMC中miRNA和mRNA表达水平明显高于无气流限制的吸烟者。miRNA和mRNA之间的调控网络可能为COPD的治疗提供潜在的靶点。
BackgroundChronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease. Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation.MethodsmiRNA and mRNA profiling of PBMCs from pooled 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated miRNAs were validated by q-PCR. The miRNA targets in dysregulated mRNAs were predicted and the pathway enrichment was analyzed.ResultsmiRNA microarray showed that 8 miRNAs were up-regulated and 3 miRNAs were down-regulated in COPD subjects compared with smokers; the upregulation of miR-24-3p, miR-93-5p, miR-320a and miR-320b and the downregulation of miR-1273 g-3p were then validated. Bioinformatic analysis of regulatory network between miRNA and mRNA showed that NOD and TLR were the most enriched pathways. miR-24-3p was predicted to regulate IL-18, IL-1β, TNF, CCL3 and CCL4 and miR-93-5p to regulate IκBα.ConclusionsThe expression of miRNA and mRNA were dysregulated in PBMCs of COPD patients compared with smokers without airflow limitation. The regulation network between the dysregulated miRNA and mRNA may provide potential therapeutic targets for COPD.
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