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Abstract：
This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking-based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-β signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD.
摘要：
本研究旨在基于生物信息学分析和体外实验证据，探讨吸烟引起的慢性阻塞性肺疾病（COPD）的发病机制。GEO,GEO2R,TargetScan,miRDB,miRWalk,大卫,和STRING数据库用于生物信息学分析。通过实时PCR和ELISA测定mRNA表达和蛋白水平。在获取数据库多样化结果的交叉点之后，四个差异表达的miRNA(hsa-miR-146a，筛选出hsa-miR-708、hsa-miR-150和hsa-miR-454)。随后，总共获得了所选择的miRNA的57个靶基因。DAVID分析结果显示，选择的miRNA通过长期增强作用参与COPD的发病机制，TGF-β信号通路，PI3K-Akt信号通路，等。STRING预测结果表明TP53、EP300和MAPK1是PPI网络的关键节点。验证性实验的结果表明,与对照组相比，ZEB1、MAPK1、EP300和SP1的mRNA表达上调,而MYB的表达下调，ZEB1，MAPK1和EP300的蛋白水平升高。一起来看,miRNAs(hsa-miR-146a,hsa-miR-708、hsa-miR-150和hsa-miR-454)及其调控的靶基因和下游蛋白分子(ZEB1、EP300和MAPK1)可能与COPD的病理过程密切相关。
