乳腺癌竞争内源性RNA网络构建与分析  

Establishment and analysis of competing endogenous RNA network for breast cancer

作　　者：褚飞 柳青峰[1] Chu Fei;Liu Qingfeng(Department of the Fifth General Surgery,People's Hospital of China Medical University,Liaoning Shenyang 110016,China)

机构地区：[1]中国医科大学人民医院第五普通外科,辽宁沈阳110016

出　　处：《现代肿瘤医学》2020年第9期1466-1471,共6页Journal of Modern Oncology

基　　金：辽宁省自然科学基金(编号:2015010272301)。

摘　　要：目的:通过对癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中的乳腺癌数据进行综合分析,寻找在乳腺癌中差异表达的长链非编码RNA(long non-coding RNA,lncRNA)、微小RNA(microRNA,miRNA)和信使RNA(messenger RNA,mRNA),构建乳腺癌竞争内源性RNA(competing endogenous RNA,ceRNA)网络,识别和预测ceRNA网络在乳腺癌中的作用。方法:下载TCGA数据库中乳腺癌组织样本基因表达谱数据,寻找差异表达的lncRNA、miRNA和mRNA,通过miRcode、miRTarB ase、TargetS can和miRDB四个数据库对差异表达的RNA之间的关系进行分析,构建以上调和下调的miRNA为中心的ceRNA网络。采用Kaplan-Meier法分析乳腺癌ceRNA网络中的lncRNA、miRNA和mRNA表达量与患者生存预后的关系,采用基因富集分析法对乳腺癌ceRNA网络中mRNA基因功能和调控通路进行分析。结果:在乳腺癌中异常表达的350个lncRNA、185个miRNA和2 928个mRNA中,分别有23个lncRNA、27个miRNA、70个mRNA参与构建乳腺癌的ceRNA网络。Kaplan-Meier生存分析显示,lncRNA MAGI2-AS3(P=0. 01)、GRIK1-AS1(P=0. 03)以及miRNA hsa-miR-301b(P=0. 01)、hsa-miR-503 (P=0. 04)和mRNA CCNE1 (P=0. 01)、KPNA2(P=0. 02)、FLI1(P=0. 02)、TGFBR2(P=0. 02)这8个基因与乳腺癌患者的生存预后显著相关。70个mRNA主要被富集到20条通路上,其中有15条通路与肿瘤有关,最显著的通路为"Pathways in cancer"。结论:ceRNA网络在乳腺癌中发挥着重要的作用,多种差异表达基因与乳腺癌预后相关,可能成为潜在的肿瘤诊断标志物和治疗靶点。Objective:To comprehensively analyze breast cancer data in the Cancer Genome Atlas(TCGA)database to find long non-coding RNAs(lncRNAs)and microRNAs that are differentially expressed in breast cancer(microRNA,miRNA),and messenger RNA(mRNA),construct a breast cancer competing endogenous RNA(ceRNA)network,and identify and predict the role of ceRNA networks in breast cancer.Methods:The gene expression profile data of breast cancer tissue samples in TCGA database were downloaded to find differentially expressed lncRNA,miRNA and mRNA.The relationship between differentially expressed RNA was analyzed by miRcode,miRTarBase,TargetScan and miRDB databases to construct the above-mentioned down-regulation miRNA-centered ceRNA network.Kaplan-Meier method was used to analyze the relationship between lncRNA,miRNA and mRNA expression in breast cancer ceRNA network and survival prognosis.The gene enrichment analysis method was used to analyze the mRNA gene function and regulatory pathway in breast cancer ceRNA network.Results:In the 350 lncRNAs abnormally expressed in breast cancer,185 miRNAs and 2928 mRNAs,23 lncRNAs,27 miRNAs and 70 mRNAs were involved in the construction of breast cancer ceRNA networks.Kaplan-Meier survival analysis showed that lncRNA MAGI2-AS3(P=0.01),GRIK1-AS1(P=0.03),and miRNA hsa-miR-301b(P=0.01),hsa-miR-503(P=0.04)and mRNA CCNE1(P=0.01),KPNA2(P=0.02),FLI1(P=0.02)and TGFBR2(P=0.02)were significantly associated with the survival prognosis of breast cancer patients.70 mRNAs were mainly enriched into 20 pathways,15 of which were associated with tumors.The most significant pathway was"Pathways in cancer".Conclusion:ceRNA network plays an important role in breast cancer.Multiple differentially expressed genes are associated with breast cancer prognosis,which may be potential targets for tumor diagnosis and treatment.

关 键 词：乳腺癌 ceRNA网络 lncRNA MIRNA TCGA数据库 

分 类 号：R737.9[医药卫生—肿瘤]