miR-639 regulates transforming growth factor beta-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting FOXC1.
Bottom Line: 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.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.
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.Show MeSH
Related in: MedlinePlus
Mentions: It has been reported that FOXC1 induces EMT in SMMC7721 cells. FOXC1 transactivates Snail expression by directly binding to the Snail promoter, thereby leading to the inhibition of E-cadherin transcription.26 We improved FOXC1 expression by transfecting TSCC cells with pcDNA3.1-FOXC1 and found that FOXC1 induced EMT in the TSCC cells (Fig. S3). The TSCC cells with high FOXC1 expression displayed a spindle shape. E-cadherin expression was reduced, while snail and vimentin expressions were increased in these cells. Furthermore, we silenced FOXC1 expression using RNA interference in SCC9 cells before TGFβ treatment (Fig.5a,b). Similar to miR-639 mimics, transfection with FOXC1-siRNA suppressed TGFβ-induced EMT in SCC9 cells. E-cadherin expression was increased and vimentin and snail expressions were reduced after FOXC1 was silenced (Fig.5a–c). These results indicate that FOXC1 might induce EMT in tongue cancer cells by transactivating snail expression. In addition, silencing FOXC1 expression reduced the invasion and migration of SCC9 (TGFβ) cells (Figs5d,S1c). Interestingly, the effect of FOXC1-siRNA alone to suppress TGFβ-induced EMT in SCC9 cells is comparable with that of the combined treatment with FOXC1-siRNA and miR-639 mimics, implying that miR-639 regulates EMT in TSCC cells via silencing FOXC1.
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.