Duan Haibo, He Huafang, Hu Qian, Lin Yingxin, Cao Shuo, Lan Xiaoshan, Li Litao, Pang Danmei
Department of Breast Cancer Medicine, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China.
Department of Radiotherapy, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China.
Exp Ther Med. 2020 Dec;20(6):245. doi: 10.3892/etm.2020.9375. Epub 2020 Oct 22.
In the present study, differences in the expression of target genes between chromatin immunoprecipitation sequencing (ChIP-seq) datasets of breast cancer MCF-7 cells treated with antibodies to E74-like factor 1 (ELF1) and cold-shock domain-containing E1 (CSDE1) were analyzed and gene regulatory networks were established. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. ELF1-associated target genes and CSDE1-associated target genes were analyzed for functional prediction and protein-protein interaction (PPI) networks. The ELF1 ChIP-seq dataset contained 95 ELF1-associated target genes, while the CSDE1 ChIP-seq dataset contained 826 CSDE1-associated target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the ELF1- and CSDE1-associated target genes had different potential functions and signaling pathways. The ELF1-associated target genes were mainly enriched in the GO terms of molecular transducer activity, catalytic activity, cellular processes and response to sensitivity, and in the KEGG pathways of olfactory transduction, the chemokine signaling pathway, carbohydrate digestion and absorption, and starch and sucrose metabolism. The CSDE1-associated target genes were mainly enriched in the GO terms of binding, transcription regulator activity, cellular processes and metabolic processes, and in the KEGG pathways of ribosome, metabolic pathways, endocytosis, oxidative phosphorylation and transcriptional misregulation in cancer. PPI network analysis revealed that the ELF1 regulatory network primarily regulated chemokine-mediated malignant tumor cells, while the CSDE1 regulatory network mainly regulated ribosomes, metabolic pathways and oxidative phosphorylation. Reverse transcription-quantitative PCR indicated that ELF1 overexpression led to significant downregulation of C-X-C motif chemokine-8 and -6 expression levels in MCF-7 cells, while overexpression of CSDE1 significantly induced the mRNA expression of CSDE1-associated target genes, which included mitochondrial ribosomal protein L4, NADH: ubiquinone oxidoreductase subunit B7, small nuclear ribonucleoprotein polypeptide E, ribosomal protein S26 (RPS26), RPS11 and RPS6, in the MCF-7 cells. In breast cancer MCF-7 cells, the target genes and regulatory pathways of ELF1 and CSDE1 were different. Understanding these regulatory pathways may help to develop strategies for personalized breast cancer treatment.
在本研究中，分析了用E74样因子1（ELF1）抗体和含冷休克结构域E1（CSDE1）抗体处理的乳腺癌MCF-7细胞的染色质免疫沉淀测序（ChIP-seq）数据集之间靶基因表达的差异，并建立了基因调控网络。这些数据集从基因表达综合数据库（GEO）下载。对ELF1相关靶基因和CSDE1相关靶基因进行功能预测和蛋白质-蛋白质相互作用（PPI）网络分析。ELF1 ChIP-seq数据集包含95个ELF1相关靶基因，而CSDE1 ChIP-seq数据集包含826个CSDE1相关靶基因。基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析表明，ELF1和CSDE1相关靶基因具有不同的潜在功能和信号通路。ELF1相关靶基因主要富集在分子转导活性、催化活性、细胞过程和对敏感性的反应等GO术语中，以及嗅觉转导、趋化因子信号通路、碳水化合物消化和吸收、淀粉和蔗糖代谢等KEGG通路中。CSDE1相关靶基因主要富集在结合、转录调节因子活性、细胞过程和代谢过程等GO术语中，以及核糖体、代谢通路、内吞作用、氧化磷酸化和癌症中的转录失调等KEGG通路中。PPI网络分析显示，ELF1调控网络主要调节趋化因子介导下的恶性肿瘤细胞，而CSDE1调控网络主要调节核糖体、代谢通路和氧化磷酸化。逆转录定量PCR表明，ELF1过表达导致MCF-7细胞中C-X-C基序趋化因子8和-6表达水平显著下调，而CSDE1过表达显著诱导了CSDE1相关靶基因的mRNA表达，这些靶基因包括线粒体核糖体蛋白L4、NADH：泛醌氧化还原酶亚基B7、小核核糖核蛋白多肽E、核糖体蛋白S26（RPS26）、RPS11和RPS6，在MCF-7细胞中。在乳腺癌MCF-7细胞中，ELF1和CSDE1的靶基因及调控通路不同。了解这些调控通路可能有助于制定个性化乳腺癌治疗策略。
