title: miR-639 regulates transforming growth factor beta-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting FOXC1.
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.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Department of Oral and Maxillofacial Surgery, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Lin
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Weiliang
authors.initials: W
authors.lastname: Chen
authors.forename: Bodu
authors.initials: B
authors.lastname: Liu
authors.forename: Youyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: Fan
authors.forename: Yilin
authors.initials: Y
authors.lastname: Li
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D014062:Tongue Neoplasms / Q000401:mortality / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; C000593699:MIRN639 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta
keywords: Epithelial-to-mesenchymal transition; FOXC1; miR-639; tongue squamous cell carcinoma; transforming growth factor beta