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

Overview

Journal Oncol Lett

Specialty Oncology

Date 2021 Mar 22

PMID 33747203

Citations 1

Authors

Dan Yang

Yaqin Fan

Beibei Xie

Jie Yang

Affiliations

Soon will be listed here.

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 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.

Citing Articles

MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways.

Entezari M, Soltani B, Sadeghizadeh M Sci Rep. 2024; 14(1):4715.

PMID: 38413784 PMC: 10899204. DOI: 10.1038/s41598-024-52940-5.

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