These authors contributed equally to this work.
miR-639 regulates transforming growth factor beta-induced epithelial–mesenchymal transition in human tongue cancer cells by targeting FOXC1
Article first published online: 29 SEP 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 105, Issue 10, pages 1288–1298, October 2014
How to Cite
Cancer Sci 105 (2014) 1288–1298
National Natural Science Foundation of China (81072225, 81272951), the Natural Science Foundation of Guangdong Province (10251008901000022), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20110171110068), Science and Technology Project of Guangzhou City (11C22060035); National Natural Science Foundation of China (81172563), Natural Science Foundation of Guangdong Province (S2011010003979); National Natural Science Foundation of China (81302369), Fundamental Research Funds for the Central Universities (13ykpy27).
- Issue published online: 22 OCT 2014
- Article first published online: 29 SEP 2014
- Accepted manuscript online: 13 AUG 2014 02:10AM EST
- Manuscript Accepted: 4 AUG 2014
- Manuscript Revised: 22 JUL 2014
- Manuscript Received: 24 MAR 2014
- National Natural Science Foundation of China. Grant Numbers: 81072225, 81272951, 81172563, 81302369
- Natural Science Foundation of Guangdong Province. Grant Numbers: 10251008901000022, S2011010003979
- Specialized Research Fund for the Doctoral Program of Higher Education of China. Grant Number: 20110171110068
- Science and Technology Project of Guangzhou City. Grant Number: 11C22060035
- Fundamental Research Funds for the Central Universities. Grant Number: 13ykpy27
- Epithelial-to-mesenchymal transition;
- tongue squamous cell carcinoma;
- transforming growth factor beta
Epithelial-to-mesenchymal transition (EMT) is implicated in embryonic development and various pathological events. Transforming growth factor beta (TGFβ) has been reported to induce EMT in tumor cells, which is a critical step in the process of metastasis leading to cancer spreading and treatment failure. However, the involvement of microRNA during the EMT process in tongue squamous cell carcinoma (TSCC) remains to be determined. To address this question, TSCC cell lines SCC9 and CAL27 were treated with human recombinant TGFβ1 for 48 h. miRNA microarray illustrated that miR-639 was significantly downregulated in TGFβ-treated SCC9 cells. Ectopic expression of miR-639 with miRNA mimics effectively blocked TGFβ-induced EMT in SCC9 and CAL27 cells, but inhibition of miR-639 in SCC9 and CAL27 cells with antisense oligonucleotides induced EMT. Computational microRNA target predictions detected a conserved sequence matching to the seed region of miR-639 in the 3′-UTR of FOXC1 mRNA. Luciferase reporter assays revealed that miR-639 targets FOXC1. Ectopic expression of FOXC1 induces EMT in TSCC cells. Silencing FOXC1 expression blocked TGFβ-induced EMT in SCC9 cells. Clinically, reduced miR-639 expression was associated with metastasis in TSCC and poor patient survival. The data from the present study suggest that reduced expression of miR-639 underscores the mechanism of TGFβ-induced EMT in TSCC by targeting FOXC1 and may serve as therapeutic targets in the process of metastasis.