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Sulforaphane inhibits human bladder cancer cell invasion by reversing epithelial-to-mesenchymal transition via directly targeting microRNA-200c/ZEB1 axis
Journal of Functional Foods ( IF 3.8 ) Pub Date : 2017-12-22 , DOI: 10.1016/j.jff.2017.12.034
Lei Huang , Bao-Long Li , Can-Xia He , Yao-Jie Zhao , Xiu-Li Yang , Bo Pang , Xiao-Hong Zhang , Yu-Juan Shan

Sulforaphane (SFN), one of the isothiocyanates, abundantly existed in quite a few of cruciferous vegetables and exhibits effective anticancer activities in our previous experiments. However, its effects on bladder cancer cell invasion and metastasis have only begun to be explored. Here, we investigated the effect of microRNA on bladder cancer cell invasion and the underlying molecular mechanism. According to the gene chip results, SFN obviously increased microRNA-200c (miR-200c) expression, one of the short noncoding RNAs that acts as considerable modulator in epithelial mesenchymal transition (EMT). Moreover, SFN dose-dependently induced EMT hallmark E-cadherin and down-regulated vimentin and transcriptional repressor ZEB1 at the level of transcription and translation, and these effects can be reversed by miR-200c inhibitor transfection. Remarkably, Transwell assay showed that cell invasiveness ability can be eradicated by silencing of ZEB1. Therefore, these findings firmly suggest that SFN inhibited bladder cancer cell invasion through reversing EMT via targeting miR-200c/ZEB1 axis.



中文翻译:

萝卜硫素通过直接靶向microRNA-200c / ZEB1轴来逆转上皮向间质转化,从而抑制人膀胱癌细胞的侵袭

萝卜硫素(SFN)是一种异硫氰酸酯,在许多十字花科蔬菜中大量存在,并且在我们之前的实验中显示出有效的抗癌活性。然而,其对膀胱癌细胞侵袭和转移的作用才刚刚被探索。在这里,我们研究了microRNA对膀胱癌细胞侵袭的影响及其潜在的分子机制。根据基因芯片结果,SFN明显增加了microRNA-200c(miR-200c)表达,microRNA-200c是短的非编码RNA之一,在上皮间充质转化(EMT)中起着重要的调节作用。此外,SFN剂量依赖性地在转录和翻译水平上诱导EMT标志性E-钙粘着蛋白和下调波形蛋白和转录阻遏物ZEB1,并且这些作用可以通过miR-200c抑制剂转染来逆转。值得注意的是,Transwell分析表明,通过沉默ZEB1可以消除细胞侵袭能力。因此,这些发现有力地表明,SFN通过靶向miR-200c / ZEB1轴逆转EMT抑制膀胱癌细胞的侵袭。

更新日期:2017-12-22
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