人体血液中衰老相关的环状RNA的初步筛选和分析

Preliminary screening and analysis of aging-related circular RNA in human blood

目的构建人类血液中环状RNA(circRNA)及mRNA的表达谱,分析血液中与衰老相关的差异表达的circRNA,预测其潜在生物学功能和通路。方法对2017年5月在首都医科大学附属北京安贞医院招募的19对祖孙(老年组和青年组)的38份血液样本进行circRNA/mRNA基因微阵列分析,筛选老年组和青年组血液标本中差异表达的circRNA/mRNA,运用基因本体论和KEGG技术分析这些circRNA涉及的生物学过程和相关信号通路,并依据ceRNA理论构建circRNA-微小RNA-mRNA网络。结果通过构建的表达谱分析比较老年组和青年组血液中circRNA的表达水平,发现了648个差异性表达的circRNA(141个circRNA上调,507个circRNA下调),959个差异表达的mRNA(230个mRNA上调,729个mRNA下调),基因本体论和KEGG分析表明,这些circRNA可能涉及JNK调节途径、细胞周期相关途径、凋亡细胞清除途径等生物学过程和癌症、碱基切除修复等相关信号通路。共筛选出89个circRNA,6个微小RNA以及59个mRNA成功构建ceRNA调控网络。结论基因微阵列分析人类血液中circRNA的表达谱,可对其进行潜在功能及通路的预测和分析,本研究可为未来circRNA和衰老的相关研究提供新靶点。

Objective To construct the expression profile of circular RNA(circRNA)and mRNA in human blood,analyze the differential expressed circRNA associated with aging in blood,and predict their potential biological functions and pathways.Methods The circRNA/mRNA gene microarray analysis was performed on 38 blood samples from 19 pairs of grandfathers and grandsons(the elderly group and the young group),who were recruited in Beijing Anzhen Hospital,Capital Medical University in May 2017.The differential expressed circRNA/mRNA in the blood samples of the elderly group and the young group were screened.The biological processes and related signaling pathways involved in these circRNA were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)technology,and the circRNA-microRNA-mRNA network was constructed based on the ceRNA theory.Results By building the expression of spectral analysis and comparison in elderly group and young group blood circRNA expression level,648 differentially expressed circRNA(141 up-regulated and 507 down-regulated)and 959 differentially expressed mRNA(230 up-regulated and 729 down-regulated)were found.GO and KEGG analysis show that these circRNA might involve biological processes such as JNK regulation pathway,cell cycle related pathway and apoptotic cell clearance pathway and cancer,base removal and repair,and other related signaling pathways.Totally 89 circRNA,6 microRNA and 59 mRNA were selected to successfully construct the ceRNA regulatory network.Conclusions Gene microarray analysis using to analyze the expression profile of circRNA in human blood can predict and analyze its potential functions and pathways.This study provides new targets for future circRNA and aging-related studies.