摘要
目的:通过生物信息学方法构建冠心病患者血液外泌体中的竞争性内源RNA(ceRNA)调控网络,探讨其发病机制。方法:在exoRbase数据库中下载冠心病患者和正常对照的血液外泌体测序数据,通过R语言分别对外泌体中mRNA、长链非编码RNA(lncRNA)、环状RNA(circRNA)的表达谱作差异表达分析,使用TargetScan和miRanda数据库共同预测和差异表达mRNA结合的微小RNA(miRNA),使用miRcode数据库预测与差异表达lncRNA结合的miRNA,使用starBase数据库预测与差异表达circRNA结合的miRNA。对3组miRNA两两取交集,保留与差异表达mRNA、lncRNA、circRNA两者及以上均结合的miRNA,构建ceRNA网络,使用Cytoscape软件可视化,并对差异表达基因进行GO富集和KEGG通路分析。结果:冠心病患者外周血外泌体中差异表达mRNA为569种,差异表达lncRNA为1408种,差异表达circRNA为282种。其中与差异表达mRNA相结合的miRNA有178种,与差异表达lncRNA结合的miRNA有207种,与差异表达circRNA结合的miRNA有328种,两两取交集,共保留120个共有的miRNA成功构建ceRNA网络,GO分析的结果主要富集在磷酸化、去磷酸化和脂质磷酸化等功能,KEGG分析的结果主要富集在甘油脂代谢和甘油磷脂代谢通路。结论:本研究成功构建冠心病患者血液外泌体中的ceRNA调控网络,为冠心病的诊断治疗提供新靶点。
Objective: We aimed to construct the competitive endogenous RNA network in peripheral blood exosome of patients with coronary heart disease, and explore its pathogenesis. Methods: The peripheral blood exosome sequencing data of patients with coronary heart disease and normal controls were downloaded from exoRbase database, and the differential expression profiles of mRNA, long non-coding RNA(lncRNA) and circular RNA(circRNA) in exosome were analyzed by R language. The micro RNA(miRNA), combined with mRNA and differentially expressed mRNA was predicted by TargetScan and miRanda database, and the miRNA combined with differentially expressed lncRNA was predicted by miRcode database. StarBase database was used to predict the miRNA combined with differentially expressed circRNA. Three groups of miRNAs were selected and intersected, and the miRNA, combined with differentially expressed mRNA, lncRNA and circRNA was retained to construct ceRNA network. Cytoscape software was used to visualize the differentially expressed genes, and the differentially expressed genes were enriched by GO and analyzed by KEGG pathway. Results: In the peripheral blood exosome of patients with coronary heart disease, there were 569 kinds of differentially expressed mRNA, 1408 kinds of differentially expressed lncRNA and 282 kinds of differentially expressed circRNA. Among them, there are 178 species of miRNAs bound to differentially expressed mRNA, 207 species of miRNA bound to differentially expressed lncRNA, 328 species of miRNA bound to differentially expressed circRNA, and a total of 120 common miRNA are retained to successfully construct ceRNA network. The results of GO analysis are mainly enriched in phosphorylation, dephosphorylation and lipid phosphorylation, while the results of KEGG analysis are mainly concentrated in glycerol metabolism and glycerol phospholipid metabolism pathway. Conclusion: In this study, we successfully constructed the ceRNA network in the blood exosome of patients with coronary heart disease, which provides a new target for the diagnosis and treatment of coronary heart disease.
作者
杨仕俊
周子华
陈芬
YANG Shijun;ZHOU Zihua;CHEN Fen(Department of Cardiology,Union Hospital.Tongji Medical College,Huazhong University of Science and Technology,Wuhan.430022,China)
出处
《临床心血管病杂志》
CAS
北大核心
2021年第7期620-625,共6页
Journal of Clinical Cardiology
