Bioinformatics approach reveals the modulatory role of JUN in atorvastatin-mediated anti-breast cancer effects.

Abstract

Atorvastatin, a widely prescribed cholesterol-lowering drug, has recently shown potential anticancer effects. However, its influence on gene expression and its biological functions in cancer, in particular breast cancer, still unclear. We aim to identify the dysregulated genes associated with atorvastatin treatment and the main players in their biological network. A total of 103 differentially expressed genes (DEGs) in the unified signature were identified, and the functional enrichment analysis suggested their relation to multiple cancer-related pathways. JUN was identified as the hub gene in the protein-protein interaction (PPI) network and was shown to be responsive to atorvastatin in breast cancer. Atorvastatin exhibited notable predicted cytotoxicity against breast cancer lines, with the activity positively correlated with JUN expression. JUN was significantly downregulated in breast cancer expression inversely correlated with cancer progression, whereas higher JUN expression was linked with better survival outcomes. Atorvastatin may directly interact with JUN protein forming a more compact and stable conformation. These findings demystify the potential therapeutic mechanism of atorvastatin in breast cancer, possibly by fine tuning of JUN expression. As such, JUN might serve as a valuable prognostic biomarker in breast cancer.