Comparison of regulatory networks of E74-like factor 1 and cold-shock domain-containing E1 in breast cancer cell lines using ChIP datasets

使用 ChIP 数据集比较乳腺癌细胞系中 E74 样因子 1 和含冷休克结构域 E1 的调控网络

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作者:Haibo Duan, Huafang He, Qian Hu, Yingxin Lin, Shuo Cao, Xiaoshan Lan, Litao Li, Danmei Pang

Abstract

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.

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