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 cellstoward tamoxifen; however, its molecular mechanism remains unclear. The purpose of this study is to identify the potentialtargets and molecular mechanisms of berberine in overcoming breast cancer resistance toward tamoxifen by using abioinformatics approach for functional network analysis. The microarray data of tamoxifen-resistant and berberine-treatedMCF-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 theDatabase for Annotation, Visualization, and Integrated Discovery revealed that several DEGs participated in the erbBtyrosine kinase signaling pathway. The analysis of protein–protein interaction network and hub gene selection by usingSTRING and Cytoscape identified the top 10 genes with the highest degree score. The analysis of genetic alterations byusing 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 overcomingbreast cancer resistance toward tamoxifen. Further studies are required to validate the results of this study