Shi Yuxia, Yang Fan, Wei Shuqing, Xu Gang
Department of Bone and Soft-Tissue Tumor, Shanxi Tumor Hospital, Taiyuan, Shanxi, China (mainland).
Department of Geriatric, Shanxi Tumor Hospital, Taiyuan, Shanxi, China (mainland).
Med Sci Monit. 2017 Apr 28;23:2042-2048. doi: 10.12659/msm.901191.
BACKGROUND The purpose of this study was to research the effects of hyperthermia on osteosarcoma (OS) by integrating the Chromatin Immunoprecipitation with the generation sequencing (ChIP-Seq) and TargetScan analysis of heat shock transcription factor 1 (HSF1). MATERIAL AND METHODS The HSF1 ChIP-seq dataset of GSE60984 was downloaded from the Gene Expressed Omnibus (GEO) database. The HSF1-binding sites were screened by MACS2 in OS cells after 10 and 20 min of hyperthermia, and they were annotated using the ChIPseeker package. The overlapped genes were selected out when HSF1-binding sites were located in the promoter region. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the overlaps. The miRNA-gene pairs of the overlaps were screened out via TargetScan, and the miRNA-gene-regulated network was constructed by Cytoscape software. RESULTS 1880 and 1283 genes of promoter regions were obtained in the osteosarcoma cells after 10 and 20 min of hyperthermia, respectively, and 889 of them were overlapped. The overlapped genes were enriched in 122 GO terms and 3 KEGG pathways. There were 13 657 pairs involved in the miRNA-gene regulated network of the overlaps. CONCLUSIONS Some biomarkers were identified for OS treated with hyperthermia. Moreover, some GO terms (regulation of programmed cell death and regulation of cell death) and pathways (p53 signaling pathway, methane metabolism, and viral myocarditis) might be involved.
背景 本研究旨在通过将染色质免疫沉淀与热休克转录因子1（HSF1）的生成测序（ChIP-Seq）及TargetScan分析相结合，研究热疗对骨肉瘤（OS）的影响。
材料与方法 从基因表达综合数据库（GEO）下载GSE60984的HSF1 ChIP-seq数据集。在热疗10分钟和20分钟后，用MACS2在骨肉瘤细胞中筛选HSF1结合位点，并用ChIPseeker软件包进行注释。当HSF1结合位点位于启动子区域时，筛选出重叠基因。利用注释、可视化和综合发现数据库（DAVID）对重叠基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。通过TargetScan筛选重叠基因的miRNA-基因对，并用Cytoscape软件构建miRNA-基因调控网络。
结果 热疗10分钟和20分钟后，骨肉瘤细胞中分别获得1880个和1283个启动子区域的基因，其中889个基因重叠。重叠基因富集于122个GO术语和3条KEGG通路。重叠基因的miRNA-基因调控网络中有13657对。
结论 鉴定出了一些热疗治疗骨肉瘤的生物标志物。此外，可能涉及一些GO术语（程序性细胞死亡调控和细胞死亡调控）和通路（p53信号通路、甲烷代谢和病毒性心肌炎）。
