期刊
ONCOLOGY LETTERS
卷 23, 期 5, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2022.13282
关键词
breast cancer; microRNA-217-5p; epithelial-mesenchymal transition; migration; metadherin; NF-kappa B signaling pathway transform
类别
资金
- Natural Science Foundation of Hebei Province [H2020206365, H2021206071]
- Special Fund for Clinical Research of Wu Jieping Medical Foundation [320.6750.2020-07-17]
- Beijing Xisike Clinical Oncology Research Foundation [Y-SY201901-0021]
miR-217-5p expression is decreased while MTDH expression is increased in breast cancer tissues. Overexpression of miR-217-5p can inhibit cell proliferation, migration, and epithelial-mesenchymal transition in breast cancer cells by suppressing the NF-kappa B signaling pathway. Furthermore, there is a negative correlation between miR-217-5p and MTDH, and restoration of MTDH expression levels can attenuate the inhibitory effects of miR-217-5p overexpression on breast cancer cell proliferation.
MicroRNAs (miRNAs) have been associated with a number of human malignancies, including breast cancer (BC). However, the expression, biological function and fundamental underlying mechanism of miR-217-5p in BC remain unclear. Therefore, in the present study, the expression levels of miR-217-5p and metadherin (MTDH) were examined in BC tissues and BC cell lines using reverse transcription-quantitative PCR. Cell Counting Kit-8 assays, cell proliferation, wound healing assays, Transwell assays and western blotting were used to examine the effects of miR-217-5p on cell proliferation, migration, the epithelial-mesenchymal transition (EMT) and NF-kappa B signaling pathway expression. The direct relationship between miR-217-5p and MTDH was assessed using a dual-luciferase reporter assay. The results demonstrated that significantly reduced expression levels of miR-217-5p but significantly increased mRNA expression levels of MTDH were observed in BC tissues from 35 patients with BC compared with non-tumor breast tissues. Furthermore, BC cell lines SK-BR3 and BT549 expressed miR-217-5p at markedly lower levels and MTDH at markedly higher levels compared with the breast epithelial MCF10A cell line. miR-217-5p overexpression significantly inhibited cell proliferation, invasion and migration and suppressed the EMT in BC cells. miR-217-5p overexpression also inhibited the NF-kappa B signaling pathway by markedly decreasing p65 mRNA and protein expression levels but significantly increasing I kappa B alpha expression levels. Furthermore, miR-217-5p knockdown markedly increased MTDH mRNA and protein expression levels. The expression levels of miR-217-5p were negatively correlated with those of MTDH in BC tissues. These results suggested that restoration of MTDH expression levels could potentially attenuate the inhibitory effects of miR-217-5p overexpression on BC cell proliferation. Therefore, in conclusion miR-217-5p overexpression may inhibit cell migration, invasion, the EMT and NF-kappa B signaling pathway in BC via targeting of MTDH. miR-217-5p may serve as an important potential target in BC therapy.
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