Open AccessmiR‐639 regulates transforming growth factor beta‐induced epithelial–mesenchymal transition in human tongue cancer cells by targeting FOXC 1
Author(s) -
Lin Zhaoyu,
Sun Lijuan,
Chen Weiliang,
Liu Bodu,
Wang Youyuan,
Fan Song,
Li Yilin,
Li Jinsong
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12499
Subject(s) - epithelial–mesenchymal transition , cancer research , ectopic expression , gene silencing , microrna , metastasis , cancer cell , biology , rna , small interfering rna , transforming growth factor beta , transfection , cell culture , transforming growth factor , microbiology and biotechnology , cancer , gene , biochemistry , genetics
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 micro RNA during the EMT process in tongue squamous cell carcinoma ( TSCC ) remains to be determined. To address this question, TSCC cell lines SCC 9 and CAL 27 were treated with human recombinant TGFβ1 for 48 h. mi RNA microarray illustrated that miR‐639 was significantly downregulated in TGF β‐treated SCC 9 cells. Ectopic expression of miR‐639 with mi RNA mimics effectively blocked TGF β‐induced EMT in SCC 9 and CAL 27 cells, but inhibition of miR‐639 in SCC 9 and CAL 27 cells with antisense oligonucleotides induced EMT . Computational micro RNA target predictions detected a conserved sequence matching to the seed region of miR‐639 in the 3′‐ UTR of FOXC 1 m RNA . Luciferase reporter assays revealed that miR‐639 targets FOXC 1 . Ectopic expression of FOXC 1 induces EMT in TSCC cells. Silencing FOXC 1 expression blocked TGF β‐induced EMT in SCC 9 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 TGF β‐induced EMT in TSCC by targeting FOXC 1 and may serve as therapeutic targets in the process of metastasis.