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MiR?28?5p inhibits the migration of breast cancer by regulating WSB2.

ABSTRACT: 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.

SUBMITTER: Ma L

PROVIDER: S-EPMC7447326 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Ma Liang L Zhang Yunfeng Y Hu Fen F

International journal of molecular medicine 20200727 4

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 w ...[more]

PMID: 32945370

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Project description:BackgroundThe involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.MethodsMiR-183 expression was quantitated in primary breast tumours, tumour associated normal tissue and breast cancer cell lines using RQ-PCR. Gain of function analysis was performed in breast cancer cells using pre-miR-183 and the effect of miR-183 overexpression on cell viability, proliferation, apoptosis and migration was examined. Customized Taqman Low Density Arrays (TLDA) were used to identify dysregulated genes in breast cancer cells transfected with pre-miR-183.ResultsWe demonstrate that miR-183 is dysregulated in breast cancer and expression correlates with estrogen receptor and HER2/neu receptor expression. Induced overexpression of miR-183 inhibited migration of breast cancer cells. This finding was substantiated by RQ-PCR of mRNA from cells overexpressing miR-183 which showed dysregulation of several migration and invasion related genes. Specifically, the VIL2-coding protein Ezrin was confirmed as a target of miR-183 and downregulation of this protein was confirmed with immunocytochemistry.ConclusionsThese findings indicate that miR-183 targets VIL2 and may play a central role in the regulation of migration and metastasis in breast cancer. Consequently, this miRNA may present an attractive target for therapeutic intervention.

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MiR?28?5p inhibits the migration of breast cancer by regulating WSB2.

Publications

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

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