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
- Dan Yang
- Yaqin Fan
- Beibei Xie
- Jie Yang
Affiliations: Faculty of Health, Yantai Nanshan University, Yantai, Shandong 265713, P.R. China, Department of Obstetrics and Gynecology, Yuncheng County People's Hospital, Heze, Shandong 274700, P.R. China
- Published online on: March 3, 2021 https://doi.org/10.3892/ol.2021.12607
Copyright: © Yang
et al. This is an open access article distributed under the
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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 underlying 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 prognosis 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 overexpression. 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.