The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2
The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2
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DOI：
10.1101/gad.1640608
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发表时间：
2008-04-01
影响因子：
10.5
通讯作者：
Peter, Marcus E.
中科院分区：
文献类型：
--
作者：
Park, Sun-Mi;Gaur, Arti B.;Peter, Marcus E.
癌症进展与胚胎发育期间发现的上皮向间充质转化（EMT）过程有相似之处，在此期间细胞下调E-钙粘蛋白并上调波形蛋白表达。通过评估由国家癌症研究所维持的药物筛选小组的60个细胞系中207个microRNA（miRNA）的表达，我们确定miR-200 miRNA家族作为表达E-cadherin但缺乏波形蛋白表达的细胞的非凡标志物。这些发现扩展到原发性卵巢癌标本。发现miR-200直接靶向E-钙粘蛋白转录抑制子ZEB 1（TCF 8/delta EF 1）和ZEB 2（SMAD相互作用蛋白1 [SIP 1]/ZFXH 1B）的mRNA。miR-200的异位表达导致癌细胞系中E-cadherin的上调并降低其运动性。相反，抑制miR-200降低E-钙粘蛋白表达，增加波形蛋白表达，并诱导EMT。我们的数据将miR-200确定为癌细胞上皮表型的有力标志物和决定因子。
Cancer progression has similarities with the process of epithelial-to-mesenchymal transition (EMT) found during embryonic development, during which cells down-regulate E-cadherin and up-regulate Vimentin expression. By evaluating the expression of 207 microRNAs (miRNAs) in the 60 cell lines of the drug screening panel maintained by the Nation Cancer Institute, we identified the miR-200 miRNA family as an extraordinary marker for cells that express E-cadherin but lack expression of Vimentin. These findings were extended to primary ovarian cancer specimens. miR-200 was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/delta EF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B). Ectopic expression of miR-200 caused up-regulation of E-cadherin in cancer cell lines and reduced their motility. Conversely, inhibition of miR-200 reduced E-cadherin expression, increased expression of Vimentin, and induced EMT. Our data identify miR-200 as a powerful marker and determining factor of the epithelial phenotype of cancer cells.