Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
Oncol Rep. 2013 Aug;30(2):643-50. doi: 10.3892/or.2013.2530. Epub 2013 Jun 7.
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 restoration 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.
微小 RNA（miRNAs）在多种生理和病理过程中发挥着重要作用，包括肿瘤转移。转移与肾癌患者的预后不良相关，几乎 20-30%的患者在诊断时就已经发生远处转移。本研究旨在探讨 miR-200c 在调节转移中的可能作用，并鉴定其在肾细胞癌（RCC）中的靶基因。在我们的组织标本微阵列中下调的 miRNAs 中，miR-200c 显著下调。功能测定表明，miR-200c 的恢复显著抑制了 SN12-PM6 和 786-0 细胞在体外的迁移和侵袭。全基因组基因表达分析和 TargetScan 数据库研究表明，ZEB1 是 miR-200c 的一个有前途的候选靶基因，它通过 E-钙黏蛋白基因沉默促进肿瘤侵袭和迁移。在 SN12-PM6 和 786-0 细胞中转染 miR-200c 后，ZEB1 下调，E-钙黏蛋白 mRNA 和蛋白上调。此外，miR-200c 影响 p-Akt 和 Akt 的蛋白表达。因此，我们的研究表明，miR-200c 通过 ZEB1 上调 E-钙黏蛋白降低肾癌细胞的转移能力，调节 miR-200c 的表达可能影响 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-200c-E-钙黏蛋白轴。
