Dang Xiaomin, Qu Xiaoyan, Wang Weijia, Liao Chongbing, Li Ying, Zhang Xiaojin, Xu Dan, Baglole Carolyn J, Shang Dong, Chang Ying
Department of Respiration, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi province, China.
Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi province, China.
Respir Res. 2017 Jan 5;18(1):4. doi: 10.1186/s12931-016-0486-5.
Chronic 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.
miRNA 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.
miRNA 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.
The 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.
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,其典型特征是单核细胞、淋巴细胞和中性粒细胞的募集增加。因此,鉴于此以及外周血单个核细胞(PBMCs)评估的便利性,近年来PBMCs的miRNA谱分析在各种疾病中受到越来越多的关注。因此,我们分析了miRNA和mRNA谱,以了解COPD患者与无气流受限的吸烟者之间的调控网络。
通过高通量微阵列检测来自17名吸烟者和14名COPD患者的PBMCs的miRNA和mRNA谱。通过q-PCR验证失调miRNA的表达。预测失调mRNA中的miRNA靶标并分析通路富集情况。
miRNA微阵列显示,与吸烟者相比,COPD患者中有8种miRNA上调,3种miRNA下调;随后验证了miR-24-3p、miR-93-5p、miR-320a和miR-320b的上调以及miR-1273 g-3p的下调。miRNA和mRNA之间调控网络的生物信息学分析表明,NOD和TLR是最富集的通路。预测miR-24-3p调控IL-18、IL-1β、TNF、CCL3和CCL4,miR-93-5p调控IκBα。
与无气流受限的吸烟者相比,COPD患者PBMCs中miRNA和mRNA的表达失调。失调的miRNA和mRNA之间的调控网络可能为COPD提供潜在的治疗靶点。