摘要
目的:构建竞争性内源核糖核酸(ceRNA)以揭示尿酸盐肾沉积分子调控机制。方法:复制尿酸盐肾沉积大鼠模型,采用高通量核糖核酸(RNA)测序技术分析尿酸盐肾沉积大鼠肾组织中微小核糖核酸(miRNA)的表达,并筛选出差异表达的miRNA。利用TargetScan、StarBase、miRDB、miRWalk 4个数据库预测miRNA的靶基因,通过DAVID和Metascape数据库对靶基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。运用Cytoscape构建主要信号通路的ceRNA调控网络。结果:测序共检测到14个差异miRNA(均为上调),该差异miRNA的靶基因主要富集在细胞衰老和癌症相关信号通路;构建获得的ceRNA调控网络含47个长链非编码RNA(lncRNA)节点、10个miRNA节点、27个信使RNA(mRNA)节点,该调控网络中miR-155-5p、miR-132-3p、miR-503-5p、miR-146b-5p和miR-212-5p为排名前5的HUB基因。结论:本研究通过筛选尿酸盐肾沉积差异miRNA,构建了尿酸盐肾沉积ceRNA网络,为尿酸盐肾沉积机制探讨提供了新思路。
Objective:To construct a competing endogenous RNA(ceRNA) network to reveal the molecular regulatory mechanism of urate deposition in kidneys.Methods:A rat model of urate deposition in kidneys was replicated.High-throughput RNA sequencing technology was used to analyze the expression of microRNAs(miRNAs) in the renal tissue of urate deposition rats,and differentially expressed miRNAs were screened.Target genes of these miRNAs were predicted using the databases TargetScan,StarBase,miRDB,and miRWalk.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the target genes were performed using the DAVID and Metascape databases.Cytoscape was used to construct the ceRNA regulatory network of the main signaling pathways.Results:Fourteen differentially expressed miRNAs were detected during sequencing(all upregulated).The target genes of these differentially expressed miRNAs were mainly enriched in signaling pathways related to cell senescence and cancer.The constructed ceRNA regulatory network consisted of 47 long non-coding RNA(lncRNA) nodes,10 miRNA nodes,and 27 messenger RNA(mRNA) nodes.In this regulatory network,miR-155-5p,miR-132-3p,miR-503-5p,miR-146b-5p,and miR-212-5p were identified as the top 5 hub genes.Conclusion:By screening differentially expressed miRNAs in urate deposition in kidneys,this study constructed a ceRNA regulatory network for urate deposition in kidneys,providing new insights into the mechanism of urate deposition in kidneys.
作者
安笑叶
毛秋月
刘泽宇
鲁程锦
张冰
林志健
王雨
AN Xiaoye;MAO Qiuyue;LIU Zeyu;LU Chengjin;ZHANG Bing;LIN Zhijian;WANG Yu(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《世界中医药》
CAS
北大核心
2024年第13期1896-1901,共6页
World Chinese Medicine
基金
国家自然科学基金青年科学基金项目(82104475)——基于ABCG2靶向分子轴探讨尿酸盐肾沉积机制及中药干预研究
国家自然科学基金联合基金项目(U20A20406)——“整合论治”策略下菊苓颗粒抗痛风病基础研究。
