Zhao Song, Niu Feng, Xu Chang-Yan, Ye Long, Bi Gui-Bin, Chen Lin, Gong Ping, Tian Gang, Nie Tian-Hong
Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Medical Records, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2015 Sep;12(3):4284-4290. doi: 10.3892/mmr.2015.3933. Epub 2015 Jun 15.
Integrative analysis of chromatin immunoprecipitation-sequencing (ChIP-seq) data and microarray data was performed to illustrate the effect of Nutlin‑3 on promoter selectivity and transcriptional regulation by the tumor suppressor p53 in U2OS human osteosarcoma cells. Raw data (accession number, GSE46642) were downloaded from Gene Expression Omnibus. Differential analyses were performed using package limma of R software. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the differentially expressed genes (DEGs) using the Database for Annotation, Visualization and Integration Discovery. Integrative analysis of ChIP‑seq data and microarray data were confirmed with ChIP‑Array. A total of 565 DEGs were identified, including 373 upregulated genes and 192 downregulated genes. Genes involved in the p53 signaling pathway, cell cycle, DNA replication, cytokine‑cytokine receptor interaction and melanoma were markedly over‑represented in the DEGs. A total of 39 DEGs were directly regulated by p53 and two were the transcription factors (TFs), E2F2 and HOXA1. E2F2 regulated 25 DEGs, while HOXA1 regulated one DEG. The cell cycle, p53 signaling pathway, melanoma and pathways involved in cancer were enriched in the direct and indirect target genes. Changes in the p53‑binding pattern induced by Nutlin‑3 were described in the present study, which may advance the understanding of the regulatory network of p53 in osteosarcoma and aid in the development of novel therapies.
进行染色质免疫沉淀测序（ChIP-seq）数据和微阵列数据的综合分析，以阐明Nutlin-3对U2OS人骨肉瘤细胞中肿瘤抑制因子p53的启动子选择性和转录调控的影响。原始数据（登录号，GSE46642）从基因表达综合数据库下载。使用R软件的limma包进行差异分析。使用注释、可视化和整合发现数据库对差异表达基因（DEG）进行基因本体富集和京都基因与基因组百科全书通路富集分析。ChIP-seq数据和微阵列数据的综合分析通过ChIP-Array得到证实。共鉴定出565个DEG，包括373个上调基因和192个下调基因。参与p53信号通路、细胞周期、DNA复制、细胞因子-细胞因子受体相互作用和黑色素瘤的基因在DEG中显著富集。共有39个DEG直接受p53调控，其中两个是转录因子（TF），即E2F2和HOXA1。E2F2调控25个DEG，而HOXA1调控1个DEG。细胞周期、p53信号通路、黑色素瘤和癌症相关通路在直接和间接靶基因中富集。本研究描述了Nutlin-3诱导的p53结合模式的变化，这可能会促进对骨肉瘤中p53调控网络的理解，并有助于开发新的治疗方法。
