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研究表明微小RNA(microRNA,miRNA)通过影响转录后基因表达来调节机体功能,并与肿瘤的发生有密切关系。然而目前癌症致病过程的转录调控网络重构大多致力于转录层面的基因表达数据的处理和分析,如何整合转录及转录后不同类型的生物数据以挖掘它们的共调控机制是目前的研究热点之一。基于此,本研究利用联合非负矩阵分解算法融合卵巢癌miRNA数据和基因表达数据形成共模块,其次对特征模块中miRNA的靶基因进行预测分析,最后对mi RNA-mRNA共模块进行转录及转录后共调控网络构建。仿真结果及分子生物学分析表明,通过联合矩阵分析方法所提取的共模块显示出了与卵巢癌致病具有显著的生物相关性和潜在的联系,此外,GO生物过程分析也进一步的揭示了所提取的共模块中miRNA靶基因的生物学功能与卵巢癌致病密切相关。
Abstract：Researches have shown that microRNA(miRNA) regulate the function of the body by affecting posttranscriptional gene expression and are closely related to tumorigenesis. However, the reconstruction of cancer pathogenic transcriptional regulatory networks is mostly focused on the processing and analysis of single gene expression data. How to integrate different types of gene expression data with miRNA data to mine the common regulatory mechanisms has become a challenging problem. Furthermore, we used the Joint Non-negative Matrix Factorization Algorithm to merge miRNA data and gene expression data of ovarian cancer to form the common module, and then predicted and analyze the miRNA target genes in the characteristic module. Finally, constructing the regulatory network of the miRNA-mRNA common module. The results of the simulation and molecular biological analysis showed that the common module extracted by the Joint Matrix Analysis showed a significant biological relevance and potential connection with ovarian cancer. In addition, GO biological process analysis further revealed that the biological function of miRNA target genes in common modules is closely related to the pathogenesis of ovarian cancer.
Bartel D.P.,2004,Micro RNAs:genomics,biogenesis,mechanism,and function,Cell,116(2):281-297
Chen J.Y.,and Zhang S.H.,2016,Integrative analysis for identifying joint modular patterns of gene-expression and drug-response data,Bioinformatics,32(11):1724-1732
Guo J.L.,2014,Mi R-137 inhibits the growth of ovarian cancer cells by targeting AEG-1,Thesis for M.S.,Harbin Medical University,Supervisor:Lou G.,pp.1-57(郭金玲,2014,mir-137靶向作用于AEG-1从而抑制卵巢癌细胞生长,硕士学位论文,哈尔滨医科大学,导师:娄阁,pp.1-57)
He X.,2007,Chemokine receptor related drug screening and signaling pathway study,Thesis for M.S.,Shanghai Institutes for Biological Sciences,Supervisor:Pei G.,pp.2-47(何幸,2007,趋化因子受体相关的药物筛选及信号通路研究,硕士学位论文,中国科学院上海生命科学研究院,导师:裴钢,pp.2-47)
Kim P.M.,and Tidor B.,2003,Subsystem identification through dimensionality reduction of large-scale gene expression data,Genome Res.,13(7):1706-1718
Kutalik Z.,Beckmann J.S.,and Bergmann S.,2008,A modular approach for integrative analysis of large-scale gene-expression and drug-response data,Nat.Biotechnol.,26(5):531-539
Lee D.D.,and Seung H.S.,1999,Learning the parts of objects by non-negative matrix factorization,Nature,401(6755):788-791
Lewis B.P.,Burge C.B.,and Bartel D.P.,2005,Conserved seed pairing,often flanked by adenosines,indicates that thousands of human genes are micro RNA targets,Cell,120(1):15-20
Liu J.Y.,Zhao Y.R.,Zhang L.N.,Yan Y.,and Zheng H.,2015,Expression and clinical significance of four mi RNAs in e-pithelial ovarian canver,Tianjin Yiyao(Tianjin Medicine Journal),43(9):996-1000(刘佳宇,赵妍蕊,张丽娜,闫晔,郑红,2015,上皮源性卵巢癌中4种mi RNAs的表达及其临床意义,天津医药,43(9):996-1000)
Mc L.R.,Friedman A.,Bigner D.,Van M.E.,and Brat D.,2008,Comprehensive genomic characterization defines human glioblastoma genes and core pathways,Nature,455(7216):1061-1068
Peng X.X.,Li Y.,Walters K.A.,Rosenzweig E.R.,Lederer S.L.,Aicher L.D.,Proll S.,and Katze M.G.,2009,Computational identification of hepatitis C virus associated micro RNA-m R-NA regulatory modules in human livers,BMC Genomics,10(1):373
Xiao L.,He C.,Li X.,Chen Y.,and Zhou J.D.,2012,Cyr61 expression influences cancer cell proliferation and apoptosis via PI3K pathway in human ovarian carcinoma cells,Zhonghua Fuchanke Zazhi(Chinese Journal of Obstetrics and Gynecology),47(8):616-620(肖兰,何婵,李欣,陈颖,周家德,2012,PI3K信号通路介导的Cyr61表达对卵巢上皮性癌细胞增殖及凋亡的影响,中华妇产科杂志,47(8):616-620)
Zhang S.H.,Li Q.J.,Liu J.,and Zhou X.J.,2011,A novel computational framework for simultaneous integration of multiple types of genomic data to identify micro RNA-gene regulatory modules,Bioinformatics,27(13):i401-i409
Zhang S.H.,Liu C.C.,Li W.,Shen H.,Laird P.W.,and Zhou X.J.,2012,Discovery of multi-dimensional modules by integrative analysis of cancer genomic data,Nucleic Acids Research,40(19):9379-9391
Zhang S.Q.,and Ng M.K.,2016,Gene-micro RNA network module analysis for ovarian cancer,BMC Systems Biology,10(Suppl 4):117
基本信息:
DOI：10.13417/j.gab.037.004227
中图分类号:R737.31
引用信息:
[1]孔薇,王慧敏,王帅群.基于miRNA-mRNA联合分析的卵巢癌调控网络构建[J].基因组学与应用生物学,2018,37(09):4227-4233.DOI:10.13417/j.gab.037.004227.
基金信息:
国家自然科学基金资助项目(NO.61271446);; 上海市科委自然科学基金项目(18ZR1417200)共同资助
2018-09-20
2018-09-20