Identification of potential gene associated with berberine in overcoming tamoxifen resistance by functional network analysis

Abstract

Previously, berberine enhanced the sensitivity ofMichigan Cancer Foundation-7 (MCF-7)-resistant breast cancer cells toward tamoxifen; however, its molecular mechanism remains unclear. The purpose of this study is to identify the potential targets and molecular mechanisms of berberine in overcoming breast cancer resistance toward tamoxifen by using a bioinformatics approach for functional network analysis. The microarray data of tamoxifen-resistant and berberine-treated MCF-7 cells were obtained from GSE67916 and GSE85871, which resulted in differentially expressed genes (DEGs). The analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment by using the Database for Annotation, Visualization, and Integrated Discovery revealed that several DEGs participated in the erbB tyrosine kinase signaling pathway. The analysis of protein-protein interaction network and hub gene selection by using STRING and Cytoscape identified the top 10 genes with the highest degree score. The analysis of genetic alterations by using cBioPortal demonstrated the genetic alterations of six potential target genes, including protein kinase C alpha type (PRKCA), epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 4 (ERBB4), amphiregulin (AREG), estrogen receptor 1 (ESR1), and STAT1. Moreover, importantly, the erbB signaling is a potential target for overcoming breast cancer resistance toward tamoxifen. Further studies are required to validate the results of this study.