Analysis of erbin gene expression regulation by micrornas in breast cancer

Abstract

Breast cancer is a heterogeneous disease characterized by distinct molecular subtypes, defined by specific gene markers and mutations associated with different prognoses and treatment responses. The ERBIN (ERBB2IP) gene encodes a basolateral scaffold/adaptor protein that maintains epithelial cell polarity and adhesion, while also regulating key signaling pathways, including MAPK and TGF-β signaling. Its expression changes across diseases, including HER2-positive breast cancer. However, the mechanisms underlying aberrant ERBIN expression levels remain poorly investigated. This study aimed to identify specific miRNAs regulating ERBIN expression in distinct breast cancer subtypes and to understand further regulatory interactions within the miRNA-ERBIN axis. ERBIN expression patterns in publicly available breast cancer patient datasets were analyzed across molecular subtypes, TP53 mutation status, and hormone receptor status to address this aim. Expression correlation analysis between ERBIN and miRNA expression, and the results from miRNA target prediction tools, identified potential miRNAs that may regulate ERBIN expression in breast cancer. These candidates were further analyzed for their expression in aggressive subgroups to evaluate their inverse association with ERBIN, considering clinical characteristics. In addition, miRNA-seq analysis following ERBIN knockdown in MDA-MB-231 cells revealed potential regulatory feedback loops between ERBIN and selected miRNAs. Overall, the results provide comprehensive insight into the post-transcriptional regulation of ERBIN in breast cancer and suggest that the miRNA-ERBIN relationships provide a potential biomarker or therapeutic target.