中国发现三阴性乳腺癌治疗新策略

　　三阴性乳腺癌与其他乳腺癌亚型相比结局较差，并且既往研究已经发现小分子核糖核酸（miR）失调及其对肿瘤进展的影响，为阐明三阴性乳腺癌机制提供了新的途径。

　　2018年10月17日，英国《自然》旗下《细胞死亡与疾病》在线发表南京医科大学第一附属医院暨江苏省人民医院王水等学者的研究报告，发现miR-3178通过靶向细胞跨膜受体蛋白编码基因NOTCH1可以抑制三阴性乳腺癌细胞的繁殖和转移。

　　该研究发现，三阴性乳腺癌miR-3178显著减少，且miR-3178低表达与三阴性乳腺癌总生存较差相关，而与非三阴性乳腺癌无关。miR-3178的异位过表达，可以抑制上皮→间质转化，从而抑制三阴性乳腺癌细胞的繁殖、浸润、转移。通过报道基因（表达水平很容易被检测的基因，可以重组入载体再导入细胞，用于指示其上游调控序列或元件调控基因表达水平高低）双荧光素酶测定法，NOTCH1被证实为miR-3178的直接靶基因。miR-3178可以减少NOTCH1表达，而NOTCH1表达恢复可以减弱miR-3178对三阴性乳腺癌细胞繁殖、转移和上皮→间质转化的抑制作用。

　　因此，该研究结果表明，miR-3178通过靶向NOTCH1可以抑制三阴性乳腺癌细胞的繁殖和转移，有望成为三阴性乳腺癌大有潜力的治疗策略。

Cell Death Dis. 2018 Oct 17;9:1059.

miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer.

Peng Kong, Lie Chen, Muxin Yu, Jing Tao, Jiawei Liu, Yue Wang, Hong Pan, Wenbin Zhou, Shui Wang.

The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.

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.

DOI: 10.1038/s41419-018-1091-y

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