Transcriptional repression of miR-200 family members by Nanog in colon cancer cells induces epithelial mesenchymal transition (EMT)
Transcriptional repression of miR-200 family members by Nanog in colon cancer cells induces epithelial mesenchymal transition (EMT)
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Nanog 在结肠癌细胞中对 miR-200 家族成员的转录抑制诱导上皮间质转化 (EMT)
DOI：
10.1016/j.canlet.2017.01.039
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发表时间：
2017-04-28
期刊：
影响因子：
9.7
通讯作者：
Wang, Rongquan
中科院分区：
文献类型：
--
作者：
Pan, Qiong;Meng, Linkun;Wang, Rongquan
Nanog是一种重要的胚胎干细胞（ESC）基因，其功能不像经典的癌基因，但需要与其他分子合作以增强致瘤活性。本研究解决的问题是Nanog与上皮-间充质转化（EMT）-间充质-上皮转化（MET）可塑性之间是否存在miRNA联系。在此，我们发现Nanog mRNA表达水平与结肠癌细胞系和人结直肠癌组织中的miR-200 c和miR-200 b表达水平呈负相关。在低Nanog结肠癌细胞中强制Nanog表达抑制miR-200 c和miR-200 b表达，而在高Nanog结肠癌细胞中干扰Nanog表达促进miR-200 c和miR-200 b表达。此外，我们证实Nanog直接抑制miR-200 c和miR-200 b基因的转录，并且miR-200 c和miR-200 b介导Nanog诱导的EMT发生。荧光素酶和ChIP测定确定Nanog直接结合到miR-200 c和miR-200 b启动子中的潜在Nanog结合位点并抑制其转录。总之，我们的研究结果表明Nanog通过直接转录机制调节miR-200簇来调节EMT-MET可塑性，Nanog-miR-200轴可能是CRC控制的良好治疗靶点。(C)2017爱思唯尔B. V.保留所有权利。
Nanog is an important embryonic stem cell (ESC) gene that does not function as a classical oncogene, but needs to cooperate with other molecules to potentiate tumorigenic activity. The question addressed by the present study was whether a miRNA link exists between Nanog and epithelial-mesenchymal transition (EMT)-mesenchymal-epithelial transition (MET) plasticity. Here, we found that Nanog mRNA expression level was inversely correlated with miR-200c and miR-200b expression levels in colon cancer cell lines and human colorectal cancer tissues. Forced Nanog expression in low-Nanog colon cancer cells inhibited miR-200c and miR-200b expression, and interfered Nanog expression in high-Nanog colon cancer cells promoted miR-200c and miR-200b expression. Furthermore, we confirmed that Nanog directly repressed transcription of the miR-200c and miR-200b genes, and miR-200c and miR-200b mediated Nanog-induced EMT occurrence. Luciferase and ChIP assays determined that Nanog bound directly to the potential Nanog binding sites in the miR-200c and miR-200b promoters and repressed their transcription. In conclusion, our findings suggest that Nanog modulates EMT-MET plasticity by regulating miR-200 clusters via a direct transcriptional mechanism, and the Nanog-miR-200 axis may be a good therapeutic target for CRC control. (C) 2017 Elsevier B.V. All rights reserved.