Integrated gene expression profiling and chromatin immunoprecipitation followed by sequencing: Analysis of the C-terminal binding protein in breast cancer.

Abstract

This study explored the possible mechanisms of the transcriptional regulatory activities of C-terminal binding protein (CtBP) and the role of CtBP in the pathogenesis of breast cancer. Microarray data of GSE36529, including three CtBP-knockdown breast cancer MCF-7 cell samples, three control knockdown samples and data of CtBP binding profile in MCF-7 cells, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened between CtBP-knockdown MCF-7 cell samples and controls. Newly developed chromatin immunoprecipitation followed by sequencing technology was used to identify the CtBP binding regions. The direct target genes of CtBP were identified using ChIP-Array software and a regulatory network was constructed, followed by gene ontology (GO) enrichment analysis of all identified DEGs and DEGs targeted by CtBP. In total, 404 DEGs were identified in CtBP-knockdown MCF-7 cell samples. These DEGs were enriched in different GO terms, such as cellular response to stress and cell cycle, endoplasmic reticulum and nucleotide binding. Additionally, 143 DEGs were identified as potential direct targets of CtBP in the regulatory network. CtBP target genes such as hypoxia up-regulated 1, BTG family member 2 and endothelin 1 were mainly related to response to hypoxia and regulation of cell proliferation. Hypoxia up-regulated 1, BTG family member 2 and endothelin 1 may be associated with the progression of breast cancer through interaction with CtBP in different biological processes. CtBP may be a therapeutic target for the treatment of breast cancer.