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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Comparison of regulatory networks of E74-like factor 1 and cold-shock domain-containing E1 in breast cancer cell
Haibo Duan1, Huafang He2, Qian Hu1
1Department of Breast Cancer Medicine, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China.
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.
Insights
This study analyzed gene regulatory networks in breast cancer cells, revealing distinct roles for ELF1 and CSDE1 in controlling gene expression. Understanding these pathways could inform personalized breast cancer treatments.
Area of Science:
- Genomics and Molecular Biology
- Cancer Research
- Bioinformatics
Background:
- Breast cancer is a complex disease with diverse molecular underpinnings.
- Identifying key regulatory factors like E74-like factor 1 (ELF1) and cold-shock domain-containing E1 (CSDE1) is crucial for understanding cancer progression.
- Gene expression analysis provides insights into cellular functions and signaling pathways involved in cancer.
Purpose of the Study:
- To compare the target genes and regulatory networks of ELF1 and CSDE1 in breast cancer MCF-7 cells.
- To establish gene regulatory networks for ELF1 and CSDE1 using ChIP-seq data.
- To explore the functional implications of ELF1 and CSDE1 target genes in breast cancer.
Main Methods:
- Utilized chromatin immunoprecipitation sequencing (ChIP-seq) datasets for ELF1 and CSDE1 from MCF-7 cells.
- Analyzed gene expression data downloaded from the Gene Expression Omnibus (GEO) database.
- Performed functional prediction, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis.
- Validated key findings using reverse transcription-quantitative PCR (RT-qPCR).
Main Results:
- Identified 95 ELF1-associated target genes and 826 CSDE1-associated target genes.
- ELF1 network primarily targets chemokine signaling pathways relevant to malignant cells.
- CSDE1 network significantly impacts ribosome biogenesis, metabolic pathways, and oxidative phosphorylation.
- ELF1 overexpression downregulated chemokine genes, while CSDE1 overexpression upregulated ribosomal protein genes.
Conclusions:
- ELF1 and CSDE1 exhibit distinct target genes and regulatory pathways in breast cancer cells.
- The ELF1 pathway is linked to chemokine signaling, potentially influencing tumor cell behavior.
- The CSDE1 pathway is associated with fundamental cellular processes like ribosome function and metabolism.
- These findings offer potential targets for developing personalized breast cancer therapies.
