American Association for Cancer Research
10780432ccr132348-sup-fig2.pdf (222.8 kB)

Supplementary Figure 2 from Regulation of Colorectal Carcinoma Stemness, Growth, and Metastasis by an miR-200c-Sox2–Negative Feedback Loop Mechanism

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journal contribution
posted on 2023-03-31, 17:21 authored by Yan-Xia Lu, Li Yuan, Xiao-Lei Xue, Min Zhou, Yan Liu, Chao Zhang, Jing-Ping Li, Lin Zheng, Min Hong, Xue-Nong Li

PDF file - 223KB, Showed that down-regulation of miR-200c promoted tumour growth and metastasis of CRC in vitro.



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.