转录因子Nanog有维持干细胞多能性及自更新的功能，参与肿瘤的发生发展。我们发现结肠癌干细胞及有转移结肠癌患者肿瘤组织内Nanog高表达及miR-200c表达下调；miR-200c刺激结肠癌干细胞Nanog表达上调及GATA4表达抑制，但miR-200c、GATA4和Nanog之间是如何调控促进结肠癌干细胞侵袭转移的机制不清。本课题拟用报告基因、EMSA、ChIP、RNA pulldown等实验，明确Nanog 结合miR-200c启动子而转录抑制其表达，miR-200c靶向GATA4 3’-UTR区转录后调控GATA4，GATA4调控Nanog增强子抑制其表达，从而证明miR-200c/GATA4/Nanog反馈环的存在；通过上述基因表达调控后结肠癌干细胞行为改变明确该反馈环在肿瘤干细胞的生物学意义。该反馈环调控结肠癌干细胞的分子机制有助于认识结肠癌侵袭转移的发生，为其防治提供新的靶标。

As a transcription factor, Nanog functions to maintain the stemness of cancer stem cells and keep their self-renewal. The present evidence indicates that Nanog is involved in the carcinogenesis and further development. We have found that Nanog was highly expressed and miR-200c was significantly reduced in colon cancer stem cells and their derived neoplastic tissues from those patients who had the metastasis. The miR-200c mimics treatment in colon cancer stem cells led to increased Nanog expression and reduced GATA4 expression. Howerver, how do miR-200c, GATA4 and Nanog integrate and balance, and further promote the invasion and metastasis of colon cancer stem cells is largely unknown. The study is aimed to confirm whether Nanog transcriptionally regulates miR-200c through binding to the proximal promoter of miR-200c, miR-200c posttranscriptionally regulates GATA4 through its binding to the 3’-UTR of GATA4 mRNA, and GATA4 inhibits Nanog expression through its binding to the enhancer of Nanog. The data will provide the evidence of 200c/GATA4/Nanog negative feed-back loop in colon cancer stem cells. Then we investigate the biological significance of 200c/GATA4/Nanog negative feed-back loop in colon cancer stem cells via observation of the change of colon cancer stem cells after modulating of the feed-back loop. The negative feed-back loop of 200c/GATA4/Nanog in colon cancer stem cells will be helpful to understand the occurrence of the neoplastic invasion and metastasis and provides the possible therapeutic targets for colon cancer.