Targeting of FK506 binding protein 5 by miR‑203 affects the progression of breast cancer via regulating the fatty acid degradation pathway and potential drug‑repurposing

Abstract

Increasing number of studies have suggested that microRNA (miR)‑203 is a potential prognostic marker for breast cancer. However, the specific molecular mechanism underlying the effects of miR‑203 remains unknown. The present study aimed to explore the molecular target and under‑ lying mechanisms of action of miR‑203 in breast cancer via bioinformatics analysis and cellular assays, such as wound healing assay and western blotting. In the present study, 17 candidate target genes of miR‑203 were identified in the downregulated differentially expressed genes from Affymetrix microarray and TargetScan 7.2 database. Subsequently, FK506 binding protein 5 (FKBP5) was considered as the miR‑203 target by 3 different hub gene analysis methods (EcCentricity, Betweenness and Stress). FKBP5 protein expression was significantly downregulated in SUM159 cells transfected with miR‑203 mimics compared with SUM159 cells transfected with miR‑203 negative control (NC) in western blot analysis. High expression of FKBP5 was associated with poor prog‑ nosis in breast cancer based on the results obtained from the Kaplan‑Meier Plotter database. In addition, the wound healing assay indicated that the inhibition of migration due to miR‑203 overexpression in SUM159 cells was reversed by FKBP5 over‑ expression. These results suggested that miR‑203 may directly target FKBP5. In addition, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that miR‑203 might play a role in breast cancer via the ‘fatty acid degradation’ KEGG pathway. Notably, the levels of fatty acids were significantly reduced in SUM159 cells transfected with miR‑203 mimics compared with SUM159 cells transfected with miR‑203 NC when assessed by the fatty acid content assay. Finally, virtual screening analysis revealed that ZINC000003944422 may be a potential inhibitor of FKBP5. In summary, the present study demonstrated that miR‑203 may directly target FKBP5 in breast cancer via fatty acid degradation and potential drugs, hence providing a novel treatment approach for breast cancer.