PDF(Pubmed)
Abstract：
Background: NOTCH receptor 3 (NOTCH3) and zinc finger E-box binding protein 1 (ZEB1) play important roles in breast cancer respectively. NOTCH3 maintains the luminal phenotype and inhibits epithelial-mesenchymal transition (EMT) in breast cancer, while ZEB1 and NOTCH3 have the opposite effects. Methods: Public databases were used to predict the expression of NOTCH3 and ZEB1 in breast cancer cell lines. The regulatory effect of NOTCH3 on ZEB1 expression was verified by western blot and RT-PCR. MiRNAs regulating ZEB1 expression were identified by using multiple databases and confirmed by reporter gene experiments. Cellular function experiments were conducted to evaluate the role of NOTCH3/miR-223/ZEB1 in the proliferation and invasion of triple-negative breast cancer (TNBC). Results: NOTCH3 and ZEB1 have opposite expression pattern in MCF-7 cells that over-express LncATB or were incubated in TGF-β to induce EMT. Western blotting and RT-PCR showed that NOTCH3 could regulate expression of ZEB1. MiR-223 inhibited the proliferation and invasion of breast cancer cells via down-regulating the expression of ZEB1. NOTCH3 inhibited the proliferation and invasion of breast cancer cells via up-regulating the expression of miR-223. Clinically, high expression of NOTCH3, miR-223 or low expression of ZEB1 were related to good prognosis of breast cancer patients. Conclusion: The current study reports a novel NOTCH3/miR-223/ZEB1 axis, which can inhibit the proliferation and invasion of breast cancer cells, and may serve as a potential biomarker for the prognosis of breast cancer.
摘要：
背景:NOTCH受体3(NOTCH3)和锌指E盒结合蛋白1(ZEB1)分别在乳腺癌中发挥重要作用。NOTCH3维持乳腺癌的管腔表型并抑制上皮-间质转化（EMT），而ZEB1和NOTCH3具有相反的效果。方法：使用公共数据库预测NOTCH3和ZEB1在乳腺癌细胞系中的表达。通过Westernblot和RT-PCR验证了NOTCH3对ZEB1表达的调节作用。通过使用多个数据库鉴定调节ZEB1表达的miRNA,并通过报告基因实验证实。进行细胞功能实验以评估NOTCH3/miR-223/ZEB1在三阴性乳腺癌（TNBC）的增殖和侵袭中的作用。结果：在过表达LncATB或在TGF-β中孵育以诱导EMT的MCF-7细胞中，NOTCH3和ZEB1具有相反的表达模式。Western印迹和RT-PCR显示NOTCH3可以调节ZEB1的表达。MiR-223通过下调ZEB1的表达抑制乳腺癌细胞的增殖和侵袭。NOTCH3通过上调miR-223的表达抑制乳腺癌细胞的增殖和侵袭。临床上,NOTCH3、miR-223高表达或ZEB1低表达与乳腺癌患者预后良好有关。结论:本研究报道了一个新的NOTCH3/miR-223/ZEB1轴,可以抑制乳腺癌细胞的增殖和侵袭，并可能作为乳腺癌预后的潜在生物标志物。
