PT  - JOURNAL ARTICLE
AU  - Lu, Yan-Xia
AU  - Yuan, Li
AU  - Xue, Xiao-Lei
AU  - Zhou, Min
AU  - Liu, Yan
AU  - Zhang, Chao
AU  - Li, Jing-Ping
AU  - Zheng, Lin
AU  - Hong, Min
AU  - Li, Xue-Nong
TI  - Regulation of Colorectal Carcinoma Stemness, Growth, and Metastasis by an <em>miR-200c</em>-Sox2–Negative Feedback Loop Mechanism
AID  - 10.1158/1078-0432.CCR-13-2348
DP  - 2014 May 15
TA  - Clinical Cancer Research
PG  - 2631--2642
VI  - 20
IP  - 10
4099  - http://clincancerres.aacrjournals.org/content/20/10/2631.short
4100  - http://clincancerres.aacrjournals.org/content/20/10/2631.full
SO  - Clin Cancer Res2014 May 15; 20
AB  - Purpose: To elucidate a novel mechanism of miR-200c in the regulation of stemness, growth, and metastasis in colorectal carcinoma (CRC). Experimental Design: Quantitative reverse transcription PCR was used to quantify miR-200c expression in CRC cell lines and tissues. A luciferase assay was adopted for the target evaluation. The functional effects of miR-200c in CRC cells were assessed by its forced or inhibited expression using lentiviruses. Results: MiR-200c was statistically lower in CRC clinical specimens and highly metastatic CRC cell lines compared with their counterparts. Sox2 was validated as a target for miR-200c. The knockdown of miR-200c significantly enhanced proliferation, migration, and invasion in CRC cell lines, whereas the upregulation of miR-200c exhibited an inverse effect. Moreover, rescue of Sox2 expression could abolish the effect of the upregulation of miR-200c. In addition, the reduction of miR-200c increased the expression of CRC stem cell markers and the sphere-forming capacity of CRC cell lines. Further study has shown that miR-200c and Sox2 reciprocally control their expression through a feedback loop. MiR-200c suppresses the expression of Sox2 to block the activity of the phosphoinositide 3-kinase (PI3K)–AKT pathway. Conclusion: Our findings indicate that miR-200c regulates Sox2 expression through a feedback loop and is associated with CRC stemness, growth, and metastasis. Clin Cancer Res; 20(10); 2631–42. ©2014 AACR.