基于生物信息学分析和构建乳腺癌脑转移中miRNA-TF-mRNA调控网络  

Based on Bioinformatics Analysis and Construction of miRNA-TF-mRNA Regulatory Network in Breast Cancer Brain Metastasis

作　　者：潘鑫 刘芷涵 刘析璘 PAN Xin;LIU Zhihan;LIU Xilin(Department of Medicine,Medical College of Jinzhou Medical University,Jinzhou 121000,Liaoning,China;Department of Medical Technology,Medical college of Jinzhou Medical University,Jinzhou 121000,Liaoning,China;Department of Nursing,Hebei Oriental University,Langfang 065000,Hebei,China)

机构地区：[1]锦州医科大学医疗学院医学系,辽宁锦州121000 [2]锦州医科大学医疗学院医学技术系,辽宁锦州121000 [3]河北东方学院护理系,河北廊坊065000

出　　处：《医学信息》2025年第6期9-14,共6页Journal of Medical Information

基　　金：国家级大学生创新创业训练计划项目(编号:202313213005)。

摘　　要：目的构建乳腺癌脑转移中miRNA-TF-mRNA调控网络。方法从GEO数据库下载乳腺癌脑转移相关的miRNA和mRNA表达数据集,通过GEO2R对数据集进行差异分析。使用miRWalk、TargetScan和miRDB工具预测差异表达miRNAs的下游靶mRNAs,并与差异表达mRNAs进行交叉匹配,同时进行GO和KEGG功能富集分析。利用String数据库构建交叉mRNAs的PPI网络图并筛选关键靶mRNAs。通过FunRich软件预测靶mRNAs的转录因子(TFs),并利用Cytoscape软件构建乳腺癌脑转移中相关的miRNA-TF-mRNA调控网络。结果共筛选出差异表达的miRNAs 54个,全为上调miRNAs。预测的下游靶mRNAs与差异表达mRNAs取交集共筛选出41个候选靶mRNAs。GO分析显示其生物过程主要参与基因表达的正调控等,分子功能主要参与涉及调控RNA聚合酶Ⅱ转录因子的活性;KEGG通路分析显示主要集中在癌症相关的Ras信号通路。String数据库构建候选靶mRNAs的PPI网络图,筛选出包括SUMO1、DAXX、UBA2、RBX1等在内的23个关键mRNAs。FunRich软件预测获得10个调控关键mRNAs的TFs,包括SMAD1、HOXA3、FOXO1等。利用Cytoscape软件构建miRNA-TF-mRNA调控网络,得到3个miRNAs节点、10个TFs节点、23个候选靶mRNAs节点。结论miR-532-3p、miR-1224-5p、miR-877-5p和SMAD1、HOXA3、FOXO1等TFs、以及SUMO1、DAXX、UBA2等关键靶mRNAs可能在乳腺癌脑转移发生发展过程中构成重要的miRNA-TF-mRNA调节网络。Objective To construct a miRNA-TF-mRNA regulatory network in brain metastasis of breast cancer.Methods The miRNA and mRNA expression data sets related to brain metastasis of breast cancer were downloaded from GEO database,and the data sets were analyzed by GEO2R.The downstream target mRNAs of differentially expressed miRNAs were predicted by miRWalk,TargetScan and miRDB tools,and cross-matched with differentially expressed mRNAs,and GO and KEGG functional enrichment analysis were performed.The PPI network diagram of cross mRNAs was constructed by String database,and the key target mRNAs were screened.The transcription factors(TFs)of target mRNAs were predicted by FunRich software,and the miRNA-TF-mRNA regulatory network related to brain metastasis of breast cancer was constructed by Cytoscape software.Results A total of 54 differentially expressed miRNAs were screened,all of which were up-regulated miRNAs.A total of 41 candidate target mRNAs were screened from the intersection of predicted downstream target mRNAs and differentially expressed mRNAs.GO analysis showed that its biological process was mainly involved in the positive regulation of gene expression,and its molecular function was mainly involved in the regulation of RNA polymeraseⅡtranscription factor activity.KEGG pathway analysis showed that it mainly focused on cancer-related Ras signaling pathways.The PPI network of candidate target mRNAs was constructed by String database,and 23 key mRNAs including SUMO1,DAXX,UBA2 and RBX1 were screened out.FunRich software predicted 10 TFs that regulate key mRNAs,including SMAD1,HOXA3,FOXO1,etc.The miRNA-TF-mRNA regulatory network was constructed by Cytoscape software,and 3 miRNAs nodes,10 TFs nodes and 23 candidate target mRNAs nodes were obtained.Conclusion miR-532-3p,miR-1224-5p,miR-877-5p,SMAD1,HOXA3,FOXO1 and other TFs,as well as SUMO1,DAXX,UBA2 and other key target mRNAs may constitute an important miRNA-TF-mRNA regulatory network in the development of brain metastasis of breast cancer.

关 键 词：乳腺癌脑转移 微小RNAS 生物信息学 miRNA-TF-mRNA调控网络 

分 类 号：R730.1[医药卫生—肿瘤]