miR-28-5p inhibits the migration of breast cancer by regulating WSB2

MicroRNAs (miRNAs or miRs) play an important role in the tumorigenesis and progression of breast cancer. However, the function of miR-28-5p in breast cancer migration has yet to be determined. In the present study, Human MicroRNA Expression Database (HMED) analysis revealed that the expression level of miR-28-5p was significantly lower in breast cancer tissue than in normal breast tissue. Kaplan -Meier plotter (KMPLOT) analysis revealed that the low expression level of miR-28-5p was associated with a poor survival in breast cancer. In addition, reverse transcription-quantitative PCR (RT-qPCR) revealed that the expression of miR-28-5p was significantly lower in breast cancer cell lines compared with that in human mammary epithelial cells (HMECs). Moreover, transfection with miR-28-5p mimics suppressed the migration of MCF-7 cells, whereas an miR-28-5p inhibitor exerted the opposite effect. Gene chip assay identified 648 differentially expressed genes (DEGs) in cells overexpressing miR-28-5p. The DEGs are enriched in the 'focal adhesion' and 'pathway in cancer' pathways. The expression levels of Ras-related protein Rap-1b (RAP1B), WD repeat and SOCS box containing 2 (WSB2) and vascular endothelial growth factor A (VEGFA) were confirmed by RT-qPCR. Furthermore, transfection with miR-28-5p mimics decreased WSB2 expression, whereas the miR-28-5p inhibitor increased the expression of WSB2, at both the transcriptional and translational levels. miR-28-5p targets the 3′UTR of WSB2, and the binding site is conserved in multiple species, with a consensus motif of 5′-AGCUCCUU-3′. Moreover, WSB2 overexpression promoted the migration of MCF-7 cells which had been inhibited by miR-28-5p. UALCAN analysis revealed that WSB2 was significantly upregulated in primary breast tumor tissue, and a high expression level of WSB2 was associated with a poor survival in breast cancer. Furthermore, immunohistochemistry revealed that the expression of WSB2 was markedly higher in breast cancer tissue compared with that in adjacent normal breast tissue. Taken together, the findings of the present study demonstrate that miR-28-5p inhibits the migration of breast cancer cells by regulating WSB2 expression, and the miR-28-5p/WSB2 axis may be a novel therapeutic target in breast cancer.