摘要
肺纤维化是一种进展的致死性呼吸系统疾病,预后较差且缺乏特效的治疗方法。研究发现,环状RNA(circular RNA,circRNA)和微小RNA(micro RNA,miRNA)作为内源性非编码RNA分子可参与多种生物学过程,在肺纤维化的发生发展中起重要作用。本研究利用基因表达综合数据库(Gene Expression Omnibus,GEO)、GEO2R工具筛选肺纤维化相关的差异表达circRNA及miRNA,使用circularRNA Interactom预测与差异表达circRNA结合的miRNA,用TargetScan、miRDB及miRWalk预测miRNA靶基因,并用DAVID对靶基因进行GO分析和KEGG功能分析,用STRING对靶基因进行蛋白质相互作用预测。结果显示,共筛选出肺纤维化相关的差异表达的circRNA、miRNA分别有18个和21个,预测了与差异表达的circRNA相互作用的miRNA及mRNA,并构建了circRNA-miRNA-mRNA相互作用网络图。DAVID基因功能富集分析发现,circRNA可能通过AMPK信号通路参与肺纤维化过程。构建蛋白质相互作用网络图发现它的10个关键节点。研究结果旨在为circRNA及miRNA在肺纤维化中的发病机制研究提供参考,为肺纤维化治疗拓宽思路。
Pulmonary fibrosis is a progressive,lethal respiratory disease with a poor prognosis and lack of specific treatment.Studies have found that circular RNA(circRNA)and microRNA(miRNA),as endogenous non-coding RNA molecules,can participate in various biological processes and play an important role in the development of pulmonary fibrosis.The Gene Expression Omnibus(GEO)and GEO2R tools were used to screen differentially expressed circRNA and miRNA related to pulmonary fibrosis.The circular RNA Interactom was applied to predict the miRNA binding sites of circRNA and the Targetscan,miRDB,and miRWalk to predict the target genes of miRNA,DAVID to perform GO and KEGG functional analysis,and STRING to perform protein-protein interactions(PPI)on predicted target genes.The results showed that we identified 18 and 21 differentially expressed circRNAs and miRNAs respectively related to pulmonary fibrosis,predicted miRNA and mRNA interacted with differentially expressed circRNAs and constructed the circRNA-miRNA-mRNA interaction network.Functional enrichment analysis of the up-regulated and downregulated circRNAs by DAVID revealed that these circRNAs may function through AMPK signaling pathway in the pathogenesis of pulmonary fibrosis.The PPI network indicated that 10 proteins might be the key nodes of the PPI network.The results of this study are expected to provide reference and broaden the thinking for the study of circRNA and miRNA in the pathogenesis and treatment of pulmonary fibrosis.
作者
刘艳萍
雷媛娣
蔡颖
袁小燕
王烨
孙站兵
邓伟华
张朝晖
LIU Yanping;LEI Yuandi;CAI Ying;YUAN Xiaoyan;WANG Ye;SUN Zhanbing;DENG Weihua;ZHANG Zhaohui(School of Public Health,University of South China,Hengyang 421001,China)
出处
《生命的化学》
CAS
CSCD
2020年第10期1850-1860,共11页
Chemistry of Life
基金
国家自然科学基金项目(81573193)
湖南省自然科学基金项目(2020JJ4082)
湖南省研究生科研创新项目(CX20200963)。
