microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis
microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis
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microRNA-200c 调节人肾细胞癌转移中的上皮间质转化
DOI：
10.3892/or.2013.2530
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发表时间：
2013-08-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Xiaoping
中科院分区：
文献类型：
--
作者：
Wang, Xuegang;Chen, Xuanyu;Zhang, Xiaoping
microRNAs（miRNAs）在肿瘤转移等生理和病理过程中发挥重要作用。转移与肾癌患者的不良预后相关，并且几乎20-30%的患者在诊断时存在远处转移。本研究旨在探讨miR-200 c在肾细胞癌（RCC）转移调控中的作用及其靶基因。在我们的组织标本微阵列中下调的miRNAs中，miR-200 c显著下调。功能分析表明，miR-200 c的抑制剂能显著抑制SN 12-PM 6和786-0细胞的体外迁移和侵袭。全基因组基因表达分析和TargetScan数据库研究表明，ZEB 1是miR-200 c的一个有希望的候选靶基因，它已被证明通过E-cadherin基因沉默促进肿瘤侵袭和迁移。miR-200 c在SN 12-PM 6和786-0细胞中的过表达与ZEB 1的下调和E-cadherin mRNA和蛋白的上调同时发生。此外，miR-200 c还影响p-Akt和Akt蛋白的表达。因此，我们的研究表明，miR-200 c通过ZEB 1上调E-cadherin降低肾癌细胞的转移能力，并且调节miR-200 c的表达可以影响Akt蛋白水平。因此，我们得出结论，在RCC的上皮-间质转化过程中存在Akt-miR-200 c-E-cadherin轴。
microRNAs (miRNAs) play essential roles in several physiological and pathological processes, including tumor metastasis. Metastasis is associated with poor prognosis in renal carcinoma patients and almost 20-30% of patients present with distant metastasis at the time of diagnosis. The aim of the present study was to investigate the possible roles of miR-200c in regulating metastasis and to identify its target genes in renal cell carcinoma (RCC). Among the miRNAs downregulated in our tissue specimen microarray, miR-200c was downregulated significantly. Functional assays demonstrated that restoratidn of miR-200c significantly inhibited the migration and invasion of SN12-PM6 and 786-0 cells in vitro. Genome-wide gene expression analysis and TargetScan database studies showed that ZEB1, which has been shown to promote tumor invasion and migration through E-cadherin gene silencing, is a promising candidate target gene of miR-200c. Overexpression of miR-200c in SN12-PM6 and 786-0 cells was concurrent with downregulation of ZEB1 and upregulation of E-cadherin mRNA and protein. In addition, miR-200c affected the protein expression of p-Akt and Akt. Thus, our study demonstrated that miR-200c decreases the metastatic ability of renal carcinoma cells by upregulating E-cadherin through ZEB1 and that modulating the expression of miR-200c could influence Akt protein levels. We therefore concluded that there is an Akt-miR-200c-E-cadherin axis in the epithelial-to-mesenchymal transition process in RCC.