基于TCGA数据库筛选与三阴型乳腺癌预后相关的miRNAs及其基因网络  

Screening of miRNAs related to prognosis of triple-negative breast cancer and its gene network based on TCGA Database

作　　者：宋玥莹 高超 陈文俊 邵艾彧 乔乙春[2] 李卓林[2] SONG Yueying;GAO Chao;CHEN Wenjun;SHAO Aiyu;QIAO Yichun;LI Zhuolin(Center for Disease Control and Prevention Institure of School Health and Prevention of Common Student Diseases,Changchun City,Jilin Province,Changchun 130033,China;Department of Epidemiology and Health Statistics,School of Public Health,Jilin University,Changchun 130021,China)

机构地区：[1]吉林省长春市疾病预防控制中心学校卫生与学生常见病防治所,吉林长春130033 [2]吉林大学公共卫生学院流行病与卫生统计学教研室,吉林长春130021

出　　处：《吉林大学学报（医学版）》2024年第2期392-399,共8页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(81702606);吉林大学白求恩计划项目(2020B16)。

摘　　要：目的:筛选与三阴型乳腺癌(TNBC)预后相关的关键微小RNA(miRNAs)及其靶基因,探讨其参与调控的生物学功能和信号通路,为TNBC患者预后标志物的筛选提供理论依据。方法:基于癌症基因组图谱(TCGA)数据库筛选TNBC患者与非TNBC患者差异表达miRNAs,通过生存分析明确与患者预后相关的miRNAs。利用miRDB和miRWalk3.0在线数据库筛选miRNAs的靶基因,Cytoscape 3.8.2软件明确miRNA-信使核糖核酸(mRNA)调控网络,利用R软件limma数据包筛选TNBC患者与非TNBC患者差异表达miRNAs,利用R软件clusterProfiler包分析靶基因参与的生物学功能和通路。结果:生存分析,miR-9、miR-17、miR-31、miR-146a、miR-188和miR-190b与TNBC患者的预后有关,且上述miRNAs表达量越低,TNBC患者预后越差。筛选出受这6种miRNAs调控的靶基因224个。基因本体论(GO)功能富集分析,靶基因主要参与乳腺腺泡的发育、DNA转录的正向调控以及血管生成等功能;京都基因与基因组百科全书(KEGG)信号通路富集分析,靶基因主要富集在细胞因子-细胞因子受体相互作用以及胰岛素分泌信号等通路。网络分析,miR-9、miR-17、溶质载体家族24成员2(SLC24A2)、vav鸟苷酸交换因子3(VAV3)、三部结构域含有36(TRIM36)、突触标记素1(SYT1)、富勒林和Sec7结构域含有3(PSD3)、过氧化物酶体增殖物活化受体α(PPARA)、RNA聚合酶Ⅲ亚基G(POLR3G)、多形性腺瘤基因1(PLAG1)、泛素相关和SH3结构域含有B(UBASH3B)及SH3结构域和四重肽重复2(SH3TC2)是调控网络中的关键基因,其中miR-9-SYT1、miR-9-KIF13B、miR-9-KITLG、miR-17-SLC24A2、miR-31-SLC24A2、miR-146a-SYT1、miR-146a-KIF13B、miR-188-SLC24A2和miR-188-SLC24A2的miRNA-mRNA相互作用最为密切。结论:miR-9、miR-17、miR-31、miR-146a、miR-188和miR-190b及其靶基因参与乳腺腺泡发育和血管生成等生理过程,与TNBC患者的不良预后密切相关。Objective:To identify the key microRNAs(miRNAs)and their target genes associated with the prognosis of triple-negative breast cancer(TNBC)and to discuss their roles in regulatory biological functions and signaling pathways,and to provide the theoretical basis for the selection of prognostic biomarkers for the patients with TNBC.Methods:The differentially expressed miRNAs between the TNBC patients and non-TNBC patients were selected based on The Cancer Genome Atlas(TCGA)Database;survival analysis was used to clarify the miRNAs related to the prognosis of the patients;miRDB and miRWalk3.0 online Databases were used to screen for the miRNA target gene;Cytoscape 3.8.2 software was used to elucidate the miRNA-messenger RNA(mRNA)regulatory network;the limma package in R software was used to screen the differentially expressed miRNAs of the TNBC patients and non-TNBC patients;the clusterProfiler package in R software was used to analyze the biological functions and pathways involved by the target genes.Results:The survival analysis results showed that miR-9,miR-17,miR-31,miR-146a,miR-188,and miR-190b were associated with the prognosis of the TNBC patients,and low expression levels of these miRNAs were correlated with the poorer prognosis of the patients.A total of 224 target genes regulated by these six miRNAs were identified.The Gene Ontology(GO)functional enrichment analysis results showed that the target genes were primarily involved in the development of mammary alveoli,positive regulation of DNA transcription,and angiogenesis.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis results showed that the target genes were mainly enriched in cytokine-cytokine receptor interaction and insulin secretion signaling pathways.The network analysis results identified the key genes in the regulatory network,including solute carrier family 24 member 2(SLC24A2),vav guanine nucleotide exchange factor 3(VAV3),tripartite motif containing 36(TRIM36),synaptotagmin 1(SYT1),pleckstrin and Sec7 domain containing 3

关 键 词：三阴型乳腺癌 微小核糖核酸 预后 调控网络 靶基因 

分 类 号：R737.9[医药卫生—肿瘤]