乳腺癌增强子-miRNA调控网络识别与分析  

Identification and Analysis of Enhancer-miRNA Regulatory Network in Breast Cancer

作　　者：钱明明 谭政堂 王文著 李昶蓥 邱正良[2] 郭志云[1] QIAN Ming-ming;TAN Zheng-tang;WANG Wen-zhu;LI Chang-ying;QIU Zheng-liang;GUO Zhi-yun(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,Sichuan,China;Laboratory Animal Center,Academy of Military Medical Sciences,Beijing 100071,China)

机构地区：[1]西南交通大学生命科学与工程学院,中国四川成都610031 [2]中国人民解放军军事医学科学院实验动物中心,中国北京100071

出　　处：《生命科学研究》2021年第1期64-69,共6页Life Science Research

基　　金：传染病防治科技重大专项(2018ZX10101-003-001-008)。

摘　　要：乳腺癌发病率位列女性恶性肿瘤之首。先前研究表明增强子可通过调控miRNA影响肿瘤的发生发展。然而,增强子与miRNA在乳腺癌中形成何种调控网络目前尚不清楚。为了探究乳腺癌中增强子与miRNA形成的调控网络,通过分析112个乳腺浸润癌样本和104个正常组织样本,共识别了220对增强子-miRNA调控关系,其中包括220个增强子、56个乳腺癌失调miRNAs。生存分析表明, 6个miRNAs (hsa-mir-195、hsa-mir-671、hsa-mir-3619、hsa-mir-4664、hsa-mir-5003、hsa-mir-5691)的表达水平显著与乳腺浸润癌患者的生存时间相关。进一步的GO/KEGG功能富集分析显示,这6个miRNAs的靶基因显著富集在癌症相关生物学进程与信号通路上。对这6个miRNAs的靶基因进行驱动基因与网络分析,共识别了6个网络关键节点,其中TP53、CCNE2的基因显著与乳腺浸润癌患者的生存时间相关。以上结果为探索增强子与miRNA在乳腺癌中的调控机制提供了理论与方法基础。The incidence of breast cancer ranks first among female malignancies.Previous studies have shown that enhancers can affect the development of tumors by regulating miRNAs.However,it is unclear what kind of regulatory network is formed between enhancers and miRNAs in breast cancer.In order to explore the regulatory network formed by breast cancer enhancers and miRNAs,220 pairs of enhancer-miRNA regulatory relationships were identified in 112 invasive breast cancer samples and 104 normal tissue samples,including220 enhancers and 56 breast cancer dysregulated miRNAs.Survival analysis showed that the expression levels of six miRNAs(hsa-mir-195,hsa-mir-671,hsa-mir-3619,hsa-mir-4664,hsa-mir-5003,hsa-mir-5691)were significantly correlated with the survival of patients with invasive breast cancer.Further GO/KEGG functional analysis showed that the target genes of these six miRNAs were significantly enriched in cancer-related biological processes and signaling pathways.The driver genes and network analysis were performed on target genes of the six miRNAs,and a total of six network key genes were identified.Among them,TP53 and CCNE2 genes were significantly related to the survival of patients with invasive breast cancer.In summary,the results provide a theoretical and methodological basis for exploring the regulatory mechanisms of enhancers and miRNAs in breast cancer.

关 键 词：癌症基因组图谱(TCGA) 乳腺癌 增强子 微RNA(miRNA) 

分 类 号：Q523.1[生物学—生物化学] R737.9[医药卫生—肿瘤]