| 引用本文: | 王立山,祝鹏飞,祁福娟,曹鑫恺,孔艳,臧卫东.基于乳腺癌ChIP-seq数据的p53抑癌机制研究[J].生物信息学,2014,12(4):. |
| WANG Lishan,ZHU Pengfei,QI Fujuan,CAO Xinkai,KONG Yan,ZANG Weidong.Molecular mechanism of p53-mediatedtumor suppressionin p53-WT breast cancerusing ChIP-seq data[J].Chinese Journal of Bioinformatics,2014,12(4):. |
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| 摘要: |
| 采用生物信息学方法分析野生型p53乳腺癌MCF7细胞的ChIP-seq(染色质免疫共沉淀-测序)数据,以揭示p53的抑癌分子机制。从NCBI下载的编号为GSE47041的ChIP-seq数据来源于三组试验,分别为：未经处理的乳腺癌MCF7细胞对照( NS_input),Nutlin-3a(一种MDM2拮抗剂)处理的MCF7细胞对照( S_input)和Nutlin-3a刺激MCF7细胞后加入p53抗体的实验组( S_p53)。 ChIP 获得的DNA数据的测序平台为Illumina HiSeq 2000。利用Bowtie参照人基因组hg19进行序列比对；利用MACS进行峰信号检测,并利用自定义软件筛选p53可能的靶基因；利用DAVID在线工具对靶基因进行通路富集分析；最后利用STRING构建蛋白互作网络。研究共得到50个p53的靶基因,其中8个靶基因( CDKN1A、BBC3、BAX、DDB2、MDM2、CCNG1、XPC和PCNA)分别富集到p53信号转导通路和核苷酸切除修复通路两个通路上。在得到的由19个靶基因构成的蛋白质相互作用网络中,连通度最高的前5个基因分别是PCNA、MDM2、REV3L、CDKN1A和BAX。研究中采用的分析ChIP-seq数据的方法能有效揭示野生型p53乳腺癌MCF7细胞中Nutlin-3a激活的p53的抑癌分子机制。 |
| 关键词: 野生型p53乳腺癌MCF7细胞 p53 ChIP-seq数据 通路富集分析 蛋白互作网络 |
| DOI：10.3969/j.issn.1672-5565.2014-04.20140404 |
| 分类号: |
| 基金项目:2013年度第二批闵行区中小企业技术创新计划项目的支持(2013MH211)。 |
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| Molecular mechanism of p53-mediatedtumor suppressionin p53-WT breast cancerusing ChIP-seq data |
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WANG Lishan, ZHU Pengfei, QI Fujuan, CAO Xinkai, KONG Yan, ZANG Weidong
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Research and Development Department of FengheShanghai Information Technology Co., Ltd., Shanghai 200241, China
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| Abstract: |
| To unveilthe molecular mechanism of p53-mediated tumor suppression in p53-WT breast cancervia analyzing ChIP-seq (chromatin immunoprecipitation-sequencing) data by bioinformatics methods. ChIP-Seq dataset GSE47041 was downloaded from Gene Expression Omnibus, which includes three groups of samples:untreatedMCF-7 cells (NS_input), MCF-7 cells treated with a Mdm2 antagonist Nutlin-3a ( S_input ) , Nutlin-3a-treated MCF-7 cells plus p53 antibody treatment (S_p53).The obtained DNA fragments were sequenced using the Illumina HiSeq 2000 platform. Sequence alignment was performed with reference to hg19 using Bowtie; peak calling was performed using MACS; a self-programmed software was used to detect p53 target genes. A total of 50 p53 target genes were predicted. Among them, eight (CDKN1A, BBC3, BAX, DDB2, MDM2, CCNG1,XPC and PCNA) were enriched in p53 signaling transduction pathway and nucleotide excision repairing pathways respectively. A protein-protein interaction network consisting of 19 target genes was obtained;PCNA, MDM2, REV3L, CDKN1A and BAX were the top five genes with the highest degrees of connection. The methods recruited to investigate the molecular mechanism underlying p53-mediated tumor suppression in p53-WT MCF-7 breast cancer cells based on ChIP-seq data are proven feasible and reliable. |
| Key words: p53-WT MCF-7 breast cancer cells p53-mediated tumor suppression ChIP-seq data Bioinformatics pathway enrichment analysis Protein-protein interaction network |
