摘要
目的筛选职业性尘肺病(以下简称“尘肺病”)患者血清中差异表达微小RNA(miRNA),通过生物信息学分析其潜在靶基因和相关转录因子。方法从谷歌学术网站检索尘肺病和miRNA的相关研究报道,选择以尘肺病病人(病例组)和正常健康人(对照组)血清样品为基础的miRNA测序或高通量芯片数据集,筛选差异表达miRNAs。采集职业性矽肺病人和健康对照人群血清样品,以实时荧光定量聚合酶链式反应法检测miRNAs相对表达水平,进行差异表达miRNAs验证。采用miRWalk数据库对筛选出的差异表达miRNAs的靶基因进行预测,对靶基因进行基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)信号通路预测和转录因子分析。结果共筛选和验证出7个差异表达的miRNAs;其中,上调的miRNAs有5个,下调的miRNAs有2个。GO富集分析和KEGG信号通路预测结果显示:上调的差异表达miRNAs主要与RNA聚合酶Ⅱ启动子转录和细胞外基质有关,主要通过黏着斑、蛋白消化和吸收、磷脂酰肌醇3-激酶/蛋白激酶B和转化生长因子-β等信号通路参与肺纤维化的发生发展;下调的2个差异表达miRNAs主要与RNA聚合酶Ⅱ启动子转录和DNA序列特异性转录因子活性有关,主要通过相关激素释放的信号通路参与肺纤维化的发生和发展。转录因子注释结果显示:SMAD家族成员3、原癌基因JUN、叉头状转录因子O1、早期生长因子1、β-连环蛋白等转录因子可能与尘肺病的发生发展有重要关联。结论筛选出的7个miRNAs在尘肺病病人血清中存在差异表达,有可能作为尘肺病的潜在生物标志物为其早期诊断、治疗和发病机制的研究提供参考。
Objective To screen the differentially expressed microRNA(miRNA)in the serum of patients with occupational pneumoconiosis(hereinafter referred to as pneumoconiosis),and explore their potential target genes and related transcription factors using bioinformatics analysis.Methods The pneumoconiosis and miRNA related reports were searched from the Google academic website.The miRNA sequencing or high-throughput microarray data sets based on the serum samplings of pneumoconiosis patients(case group)and normal healthy individuals(control group)were selected to screen for the differentially expressed miRNAs.Serum samples of patients with occupational silicosis and healthy controls were collected,and the relative expression of miRNAs was detected by real-time fluorescence quantitative polymerase chain reaction to verify the differential expression of miRNAs.The target genes of the differentially expressed miRNAs were predicted in the database of miRWalk,analyzed by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway prediction.The transcription factor analysis of target genes was carried out by the database for annotation.Results Seven differentially expressed miRNAs were screened out and verified.Among them,five were up-regulated and two were downregulated.GO enrichment analysis and KEGG signaling pathway prediction showed that the up-regulated differentially expressed miRNAs were mainly related to RNA polymeraseⅡpromoter transcription and extracellular matrix,and were mainly involved in the occurrence and development of pulmonary fibrosis through adhesion plaque,protein digestion and absorption,phosphatidylinositol 3-kinase/protein kinase B and transforming growth factor-βsignaling pathways.The down-regulated differentially expressed miRNAs were mainly related to the transcription of RNA polymeraseⅡpromoter and the activity of DNA sequence specific transcription factors,that were mainly involved in the occurrence and development of pulmonary fibrosis through the signa
作者
杨果
祁远梦
杨培琰
李超
魏静静
姚武
郝长付
YANG Guo;QI Yuan-meng;YANG Pei-yan;LI Chao;WEI Jing-jing;YAO Wu;HAO Chang-fu(School of Public Health,Zhengzhou University,Zhengzhou,Henan 450001,China)
出处
《中国职业医学》
CAS
北大核心
2021年第2期127-134,共8页
China Occupational Medicine
基金
国家自然科学基金(81773404)。
关键词
尘肺病
矽肺
肺纤维化
血清
MIRNA
差异表达
转录因子
生物信息学
Pneumoconiosis
Silicosis
Pulmonary fibrosis
Serum
miRNA
Differentially expression
Transcription factor
Bioinformatics
