miR-639 regulates transforming growth factor beta-induced epithelial–mesenchymal transition in human tongue cancer cells by targeting FOXC1

Authors

  • Zhaoyu Lin,

    1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    2. Department of Oral and Maxillofacial Surgery, Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Lijuan Sun,

    1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    2. Breast Tumor Center, Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Weiliang Chen,

    Corresponding author
    1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    2. Department of Oral and Maxillofacial Surgery, Sun Yat-sen University, Guangzhou, China
    3. Oral and Cranio-maxillofacial Surgery Center, Sun Yat-sen University, Guangzhou, China
    • Correspondence

      Jinsong Li and Weiliang Chen, Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China.

      Tel: +86-0208-1332220; Fax: +86-0208-1332425;

      E-mails: lijinsong1967@163.com and drchen@vip.163.com

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  • Bodu Liu,

    1. Breast Tumor Center, Sun Yat-sen University, Guangzhou, China
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  • Youyuan Wang,

    1. Department of Oral and Maxillofacial Surgery, Sun Yat-sen University, Guangzhou, China
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  • Song Fan,

    1. Department of Oral and Maxillofacial Surgery, Sun Yat-sen University, Guangzhou, China
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  • Yilin Li,

    1. Xaverian Brothers High School, Xaverian, Massachusetts, USA
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  • Jinsong Li

    Corresponding author
    1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    2. Department of Oral and Maxillofacial Surgery, Sun Yat-sen University, Guangzhou, China
    3. Oral and Cranio-maxillofacial Surgery Center, Sun Yat-sen University, Guangzhou, China
    • Correspondence

      Jinsong Li and Weiliang Chen, Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China.

      Tel: +86-0208-1332220; Fax: +86-0208-1332425;

      E-mails: lijinsong1967@163.com and drchen@vip.163.com

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  • Funding Information

    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).

Abstract

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.

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