Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, Jiangsu, China.
Cell Death Dis. 2018 Oct 17;9(11):1059. doi: 10.1038/s41419-018-1091-y.
Triple-negative breast cancer (TNBC) has a poorer outcome than other subtypes of breast cancer, and the discovery of dysregulated microRNA (miRNA) and their role in tumor progression has provided a new avenue for elucidating the mechanism involved in TNBC. In this study, we identified that miR-3178 was significantly reduced in TNBC, and the low miR-3178 expression correlated with poor overall survival in TNBC but not in non-TNBC. The ectopic overexpression of miR-3178 suppressed TNBC cell proliferation, invasion, and migration by inhibiting the epithelial-to-mesenchymal (EMT) transition. Notch1 was validated as the direct target gene of miR-3178, which was confirmed by the dual-luciferase reporter assay. miR-3178 decreased the expression of Notch1 and restoration of Notch1 expression attenuated the inhibitory effects of miR-3178 on cell proliferation, metastasis, and the EMT in TNBC. miR-3178 inhibited cell proliferation and metastasis by targeting Notch1 in TNBC, and the restoration of miR-3178 might be a potential therapeutic strategy for TNBC.
三阴性乳腺癌（TNBC）的预后比其他乳腺癌亚型差，而失调 microRNA（miRNA）的发现及其在肿瘤进展中的作用为阐明 TNBC 中涉及的机制提供了新的途径。在这项研究中，我们发现 miR-3178 在 TNBC 中显著下调，并且低 miR-3178 表达与 TNBC 患者的总生存不良相关，但与非 TNBC 患者无关。miR-3178 的异位过表达通过抑制上皮-间充质（EMT）转化抑制 TNBC 细胞增殖、侵袭和迁移。Notch1 被验证为 miR-3178 的直接靶基因，这通过双荧光素酶报告基因检测得到证实。miR-3178 降低了 Notch1 的表达，并且 Notch1 的恢复减弱了 miR-3178 对 TNBC 中细胞增殖、转移和 EMT 的抑制作用。miR-3178 通过靶向 TNBC 中的 Notch1 抑制细胞增殖和转移，恢复 miR-3178 可能是治疗 TNBC 的一种潜在策略。
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