Transcriptional repression of miR-200 family members by Nanog in colon cancer cells induces epithelial–mesenchymal transition (EMT)

Publication date: 28 April 2017
Source:Cancer Letters, Volume 392
Author(s): Qiong Pan, Linkun Meng, Jun Ye, Xiaolong Wei, Yangyang Shang, Yin Tian, Yonghong He, Zhihong Peng, Lei Chen, Wensheng Chen, Xiuwu Bian, Rongquan Wang
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.



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