Sulforaphane inhibits human bladder cancer cell invasion by reversing epithelial-to-mesenchymal transition via directly targeting microRNA-200c/ZEB1 axis
Sulforaphane inhibits human bladder cancer cell invasion by reversing epithelial-to-mesenchymal transition via directly targeting microRNA-200c/ZEB1 axis
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DOI：
10.1016/j.jff.2017.12.034
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发表时间：
2018-02
影响因子：
5.6
通讯作者：
Lei Huang;Baolong Li;Canxia He;Yao-Jie Zhao;Xiuli Yang;B. Pang;Xiaohong Zhang;Yujuan Shan
中科院分区：
文献类型：
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作者：
Lei Huang;Baolong Li;Canxia He;Yao-Jie Zhao;Xiuli Yang;B. Pang;Xiaohong Zhang;Yujuan Shan
萝卜硫素（sulforaphan， SFN）是异硫氰酸酯中的一种，大量存在于十字花科蔬菜中，在我们以往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影响才刚刚开始探索。在此，我们研究了microRNA在膀胱癌细胞侵袭中的作用及其分子机制。根据基因芯片结果，SFN明显增加了microRNA-200c （miR-200c）的表达，miR-200c是上皮间充质转化（EMT）中起重要调节作用的短链非编码rna之一。此外，SFN在转录和翻译水平上剂量依赖性地诱导EMT标志E-cadherin、下调vimentin和转录抑制因子ZEB1，这些作用可以通过转染miR-200c抑制剂逆转。值得注意的是，Transwell实验表明，沉默ZEB1可以消除细胞的侵袭能力。因此，这些发现有力地表明，SFN通过靶向miR-200c/ZEB1轴逆转EMT，从而抑制膀胱癌细胞的侵袭。
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.