| Objective: To investigate the expression level of MiR-25-3p in triple-negative breast cancer(TNBC)tissue samples and cell lines,and further explore the biological functions and related molecular mechanisms of MiR-25-3p in the development of triple negative breast cancer.Materials and methods: To identify differentially expressed miRNAs in TNBC,we performed miRNA microarray assay to examine the miRNA expression profiles TNBC and adjacent normal tissues samples.Among the differentially expressed miRNAs,miR-25-3p was upregulated by more than 2-folds in TNBC.Differential expression of miR-25-3p in TNBC was measured with quantitative real-time PCR(qRT-PCR)in both TNBC tissues and cell lines and was validated in the Cancer Genome Atlas(TCGA)database.The effects of miR-25-3p on proliferation,apoptosis capacity of TNBC were evaluated using Cell counting kit-8,colony formation assay and Annexin V-FITC/PI analyses.The tumor growth in vivo was observed in xenograft model.Luciferase reporter assay,qPCR and western blot were performed to validate a potential target of miR-25-3p in TNBC.Involvement of the AKT and MAPK pathways was investigated by western blot.Results: 1.MiR-25-3p was found to be upregulated in TNBC tissue samples,cell lines and TCGA Database.2.MiR-25-3p promoted TNBC cell proliferation in vitro and tumor growth in xenograft model,while suppression of miR-25-3p induced cell apoptosis.3.The luciferase reporter assay confirmed that B-cell translocation gene 2(BTG2) might be a direct target of miR-25-3p,and its expression was negatively regulated by miR-25-3p.4.Inhibition of BTG2 expression accounted for the role of miR-25-3p in TNBC.5.BTG2 suppression might indirectly activate the AKT and ERK-MAPK signaling pathways to mediate the downstream effects of miR-25-3p.Conclusions: This study demonstrates that miR-25-3p promotes proliferation by targeting tumor suppressor BTG2 and may identify new diagnostic and therapeutic targets in TNBC. |
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