[1]张 政,卢鸿健,李明慧,等.基于生物信息学分析肝细胞癌中lncRNA-miRNA-mRNA的调控网络[J].医学信息,2023,36(06):1-7.[doi:10.3969/j.issn.1006-1959.2023.06.001]
　ZHANG Zheng,LU Hong-jian,LI Ming-hui,et al.Analysis of lncRNA-miRNA-mRNA Regulatory Network in Hepatocellular Carcinoma Based on Bioinformatics[J].Journal of Medical Information,2023,36(06):1-7.[doi:10.3969/j.issn.1006-1959.2023.06.001]
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基于生物信息学分析肝细胞癌中lncRNA-miRNA-mRNA的调控网络()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年06期
页码:
1-7
栏目:
生物信息学
出版日期:
2023-03-15

文章信息/Info

Title:
Analysis of lncRNA-miRNA-mRNA Regulatory Network in Hepatocellular Carcinoma Based on Bioinformatics
文章编号:
1006-1959（2023）06-0001-07
作者:
张 政; 卢鸿健; 李明慧; 等
（1.华北理工大学临床医学院/河北省医工融合精准医疗重点实验室，河北 唐山 063000；2.华北理工大学基础医学院/河北省慢性疾病基础医学重点实验室，河北 唐山 063210）
Author(s):
ZHANG Zheng; LU Hong-jian; LI Ming-hui; et al.
(1.School of Clinical Medicine,North China University of Science and Technology/Hebei Provincial Key Laboratoryof Medical-Industrial Integration Precision Medicine,Tangshan 063000,Hebei,China; 2.School of Basic Medicine,North China University of Science and Technology/Hebei Provincial Key Laboratory of Chronic Disease,Tangshan 063210,Hebei,China)
关键词:
肝细胞癌; 生物信息学; 调控网络; 差异表达基因
Keywords:
Hepatocellular carcinoma; Bioinformatics; Regulatory network; Differentially expressed genes
分类号:
R735.7
DOI:
10.3969/j.issn.1006-1959.2023.06.001
文献标志码:
A
摘要:
目的 生物信息学方法分析肝细胞癌（HCC）中差异表达的lncRNA、miRNA和mRNA并构建相关调控网络。方法 采用R软件分析癌症基因组图谱（TCGA）数据库中374例HCC组织与50例癌旁组织中差异表达的基因，FunRich软件分析差异表达miRNAs的转录因子，FunRich软件结合Starbase和MiRDB数据库分析miRNAs的靶基因，预测的靶基因与差异表达的mRNAs进行交叉匹配；通过基因本体（GO）和京都基因与基因组百科全书（KEGG）对mRNAs和miRNAs进行功能富集分析；使用STRING数据库和Cytoscape软件构建蛋白-蛋白互作图（PPI）；Starbase数据库分析miRNAs的上游lncRNAs，Cytoscape软件构建lncRNA-miRNA-mRNA调控网络。结果 共筛选出差异表达的lncRNAs 2850个、miRNAs 38个、mRNAs 4455个；38个差异表达的miRNAs预测到201个转录因子，其中EGR1差异最显著；预测得到的mRNAs与差异表达的mRNAs取交集获得286个候选靶基因，与差异表达的miRNA-mRNA匹配后，最后筛选出交叉表达负调控的miRNAs 12个和mRNAs 108个；GO分析显示38个miRNAs生物过程（BP）主要参与血管内皮细胞和增殖迁移的调节，分子功能（MF）主要涉及mRNA结合参与转录后基因沉默；108个mRNAs的BP主要涉及胚胎器官发育、MAP激酶活性的调节，MF主要参与DNA结合转录激活物活性；KEGG通路中miRNAs主要参与对癌症的作用，mRNAs主要调节干细胞多能性。12个miRNAs的上游lncRNAs 221个，与差异表达lncRNAs交叉匹配后获得交叉表达负调控的miRNAs 2个和lncRNAs 5个，与匹配的mRNAs构建lncRNA-miRNA-mRNA的调控网络。结论 通过生物信息学对HCC中差异基因和关键基因进行分析，筛选出差异表达的lncRNAs 5个、miRNAs 2个、mRNAs 108个，成功构建了lncRNA-miRNA-mRNA的调控网络，为阐明肝细胞癌的早期诊断和预后监测标志物提供依据。
Abstract:
Objective To analyze the differentially expressed lncRNA, miRNA and mRNA in hepatocellular carcinoma (HCC) by bioinformatics methods and construct the related regulatory network.Methods The differentially expressed genes in 374 HCC tissues and 50 normal liver tissues in the Cancer Genome Atlas (TCGA) database were analyzed by R software. Funrich software was used to analyze the transcription factors of differentially expressed miRNAs. Funrich software combined with Starbase and MiRDB databases were performed to analyze the target genes of miRNAs, which was cross matched with differentially expressed mRNAs. Functional enrichment analysis of mRNAs and miRNAs was performed by Gene Ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG). STRING database and Cytoscape software were used to construct protein-protein interaction map. The upstream lncRNAs of miRNAs were analyzed by Starbase database, and the regulatory network of lncRNA-miRNA-mRNA was constructed by Cytoscape software.Results A total of 2850 lncRNAs, 38 miRNAs and 4455 mRNAs were differentially expressed in HCC. The prediction of 38 differentially expressed miRNAs resulted in a total of 201 transcription factors, of which EGR1 was the most significant. 286 candidate target genes were obtained by intersection of predicted mRNAs and differentially expressed mRNAs. The intersection of predicted mRNAs and differentially expressed mRNAs yielded 286 candidate target genes. After matching with differentially expressed miRNA-mRNAs, 12 miRNAs and 108 mRNAs with negative regulation of cross-expression were finally screened. GO showed that the biological processes (BP) of 38 miRNAs was mainly involved in the regulation of vascular endothelial cell proliferation and migration, and the molecular function (MF) was mainly involved in mRNA binding and post transcriptional gene silencing. The BP of 108 mRNAs was mainly involved in the development of embryonic organs and the regulation of MAP kinase activity, and the MF was mainly involve the activity of DNA binding transcriptional activators. miRNAs in the KEGG pathway were mainly involved in the role of cancer and mRNAs mainly regulated stem cell pluripotency. A total of 221 upstream lncRNAs of 12 miRNAs were screened, and after cross matching with differentially expressed lncRNAs, 2 miRNAs and 5 lncRNAs with negative cross expression regulation were obtained, and the regulatory network of lncRNA-miRNA-mRNA was constructed with matched mRNAs.Conclusion Through bioinformatics analysis of differential genes and key genes in HCC, 5 differentially expressed lncRNAs, 2 miRNAs and 108 mRNAs were screened out, and the regulatory network of lncRNA-miRNA-mRNA was successfully constructed, which provides a basis for clarifying the early diagnosis and prognostic monitoring markers of HCC.

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更新日期/Last Update: 1900-01-01