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

Ma,Liang; Ma,Liang; Zhang,Yunfeng; Zhang,Yunfeng; Hu,Fen; Hu,Fen

doi:10.3892/ijmm.2020.4685

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

Authors:
- Liang Ma
- Yunfeng Zhang
- Fen Hu
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Affiliations: College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China, Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China
Published online on: July 27, 2020 https://doi.org/10.3892/ijmm.2020.4685
Pages: 1562-1570
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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1	Hunter KW, Crawford NP and Alsarraj J: Mechanisms of metastasis. Breast Cancer Res. 10:S22008. View Article : Google Scholar :
2	Shi M and Guo N: MicroRNA expression and its implications for the diagnosis and therapeutic strategies of breast cancer. Cancer Treat Rev. 35:328–334. 2009. View Article : Google Scholar : PubMed/NCBI
3	Teoh SL and Das S: The role of MicroRNAs in diagnosis, prognosis, metastasis and resistant cases in breast cancer. Curr Pharm Des. 23:1845–1859. 2017. View Article : Google Scholar : PubMed/NCBI
4	Bertoli G, Cava C and Castiglioni I: MicroRNAs: New biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics. 5:1122–1143. 2015. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Pei Y, Wang X and Zhang X: Predicting the fate of microRNA target genes based on sequence features. J Theor Biol. 261:17–22. 2009. View Article : Google Scholar : PubMed/NCBI
7	Schneider C, Setty M, Holmes AB, Maute RL, Leslie CS, Mussolin L, Rosolen A, Dalla-Favera R and Basso K: MicroRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas. Proc Natl Acad Sci USA. 111:8185–8190. 2014. View Article : Google Scholar : PubMed/NCBI
8	Zhou SL, Hu ZQ, Zhou ZJ, Dai Z, Wang Z, Cao Y, Fan J, Huang XW and Zhou J: Mir-28-5p-IL-34-macrophage feed-back loop modulates hepatocellular carcinoma metastasis. Hepatology. 63:1560–1575. 2016. View Article : Google Scholar : PubMed/NCBI
9	Wang C, Wu C, Yang Q, Ding M, Zhong J, Zhang CY, Ge J, Wang J and Zhang C: Mir-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B. Oncotarget. 7:73888–73902. 2016. View Article : Google Scholar : PubMed/NCBI
10	Almeida MI, Nicoloso MS, Zeng L, Ivan C, Spizzo R, Gafà R, Xiao L, Zhang X, Vannini I, Fanini F, et al: Strand-Specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells. Gastroenterology. 142:886–896. 2012. View Article : Google Scholar : PubMed/NCBI
11	Lv Y, Yang H, Ma X and Wu G: Strand-Specific miR-28-3p and miR-28-5p have differential effects on nasopharyngeal cancer cells proliferation, apoptosis, migration and invasion. Cancer Cell Int. 19:1872019. View Article : Google Scholar : PubMed/NCBI
12	Hu F, Zhang Y, Li M, Bai Y and Zhang X: Expression and role of HEPIS in breast cancer. Oncol Lett. 18:6648–6656. 2019.PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
14	Hu F, Zhang Y, Li M, Zhao L, Chen J, Yang S and Zhang X: BMP-6 inhibits the metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression. Oncol Rep. 35:1823–1830. 2016. View Article : Google Scholar : PubMed/NCBI
15	Hu F, Gou L, Liu Q, Zhang W, Luo M and Zhang X: G-Patch domain containing 2, a gene highly expressed in testes, inhibits nuclear factor-kappaB and cell proliferation. Mol Med Rep. 11:1252–1257. 2015. View Article : Google Scholar
16	Liu Q, Song YJ, Meng LJ, Hu F, Gou LX, Jia CH, Tang HM, Wang WJ, Li M, Zhang XJ and Jia MC: Role of LM23 in cell proliferation and apoptosis and its expression during the testis development. Asian J Androl. 15:539–544. 2013. View Article : Google Scholar : PubMed/NCBI
17	Zhao F, Pan S, Gu Y, Guo S, Dai Q, Yu Y and Zhang W: Small activating RNA restores the activity of the tumor suppressor HIC-1 on breast cancer. PLoS One. 9:e864862014. View Article : Google Scholar : PubMed/NCBI
18	Gong J, Wu Y, Zhang X, Liao Y, Sibanda VL, Liu W and Guo AY: Comprehensive analysis of human small RNA sequencing data provides insights into expression profiles and miRNA editing. RNA Biol. 11:1375–1385. 2014. View Article : Google Scholar
19	Chandrashekar DS, Bashel B, Balasubramanya SA, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BV and Varambally S: UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 19:649–658. 2017. View Article : Google Scholar : PubMed/NCBI
20	Lanczky A, Nagy A, Bottai G, Munkácsy G, Szabó A, Santarpia L and Győrffy B: MiRpower: A web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 160:439–446. 2016. View Article : Google Scholar : PubMed/NCBI
21	Xiao F, Cheng Z, Wang P, Gong B, Huang H, Xing Y and Liu F: MicroRNA-28-5p inhibits the migration and invasion of gastric cancer cells by suppressing AKT phosphorylation. Oncol Lett. 15:9777–9785. 2018.PubMed/NCBI
22	Yang M, Yao Y, Eades G, Zhang Y and Zhou Q: MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism. Breast Cancer Res Treat. 129:983–991. 2011. View Article : Google Scholar : PubMed/NCBI
23	Bao Y, Wang S, Xie Y, Jin K, Bai Y and Shan S: MiR-28-5p relieves neuropathic pain by targeting Zeb1 in CCI rat models. J Cell Biochem. 119:8555–8563. 2018. View Article : Google Scholar : PubMed/NCBI
24	Neer EJ, Schmidt CJ, Nambudripad R and Smith TF: The ancient regulatory-protein family of WD-repeat proteins. Nature. 371:297–300. 1994. View Article : Google Scholar : PubMed/NCBI
25	Poujade FA, Mannion A, Brittain N, Theodosi A, Beeby E, Leszczynska KB, Hammond EM, Greenman J, Cawthorne C and Pires IM: WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer. Br J Cancer. 118:1229–1237. 2018. View Article : Google Scholar : PubMed/NCBI
26	Zhang Y, Li Z, Zhao W, Hu H, Zhao L, Zhu Y, Yang X, Gao B, Yang H, Huang Y and Song X: WD repeat and SOCS box containing protein 2 in the proliferation, cycle progression, and migration of melanoma cells. Biomed Pharmacother. 116:1089742019. View Article : Google Scholar : PubMed/NCBI
27	Nara H, Onoda T, Rahman M, Araki A, Juliana FM, Tanaka N and Asao H: Regulation of interleukin-21 receptor expression and its signal transduction by WSB-2. Biochem Biophys Res Commun. 392:171–177. 2010. View Article : Google Scholar : PubMed/NCBI