Molecular mechanism of triple-negative breast cancer-associated BRCA1 and the identification of signaling pathways

Abstract

BRAC1 has multiple important interactions with triple-negative breast cancer, the specific molecular characteristics of this interaction, however, have not yet been completely elucidated. By examining cell signaling pathways, important information for comprehending the potential mechanisms of this cancer may become known. The aim of the present study was to identify the effects of BRAC1 and to find the signaling pathway(s) involved in the pathogenic mechanism of triple-negative breast cancer. In this study, GSE27447 microarray data were obtained from the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information, and differentially expressed genes (DEGs) from GSE27447 were distinguished by Significant Analysis of Microarray. Gene ontology (GO) analysis was carried out on 132 upregulated and 198 downregulated genes with DAVID. The signaling was forecast by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors were recognized by TFatS. The BRAC1 relevant protein-protein interaction networks (PPI) were fixed by STRING and visualized by CytoScape. Overall, the upregulated DEGs, which included CR2, IGHM, PRKCB, CARD11, PLCG2, CD79A, IGKC and CD27, were primarily enriched in the terms associated with immune responses, and the downregulated DEGs, which included STARD3, ALDH8A1, SRD5A3, CACNA1H, UGT2B4, SDR16C5 and MED1, were primarily enriched in the hormone metabolic process. In addition, 13 pathways, such as the B-cell receptor-signaling pathway, the hormone synthesis signaling pathway and the oxytocin-signaling pathway, were chosen. MYC, SP1 and CTNNB1 were determined to be enriched in triple-negative breast cancer. A total of 8 genes were identified to be downregulated in the BRAC1-related PPI network. The results of the present study show a fresh angle on the molecular mechanism of triple-negative breast cancer and indicate a possible target for its treatment.

Keywords: differentially expressed genes; gene ontology analysis; protein-protein interaction network; signaling pathway; triple-negative breast cancer.

Figure 1.

B-cell receptor pathway, which may be dysregulated in TNBC. Red boxes indicate upregulated genes, purple boxes indicate no differentially expressed genes. TNBC, triple negative breast cancer.

Figure 2.

MAPK signaling pathway, which may be dysregulated in TNBC. Red boxes denote upregulated genes, and blue boxes denote downregulated genes, green and pink boxes represent indicate no differentially expressed genes. TNBC, triple negative breast cancer.

Figure 3.

mTOR signaling pathway, which may be dysregulated in TNBC. Red boxes indicate upregulated genes and blue boxes indicate downregulated genes and green and pink boxes represent indicate no differentially expressed genes.

Figure 4.

The expression of DEGs and transcription factors. (A) RT-qPCR confirmed the result of upregulated genes' mRNA expression (n=3). *P<0.05. (B) RT-qPCR confirmed the result of downregulated genes' mRNA expression (n=3). *P<0.05. (C) Western blot confirmed the result of TFs. RT-qPCR, reverse transcription-quantitative polymerase chain reaction; DEG's differentially expressed genes; TF, transcription factor.

Figure 5.

BRCA1 related protein-protein interaction network. The interaction network was predicated by STRING and visualized by Cytoscape software. Red indicates upregulated genes and green indicates downregulated genes and yellow indicates no differentially expressed genes.