Abstract: PURPOSE:The aim of this study was to investigate the mechanism of miR-181a regulating epithelial-mesenchymal transition (EMT) and enhancing the capacity of cisplatin-resistance of tongue squamous cell carcinoma cells. METHODS: TSCC CDDP resistant cell line CAL27/CDDP and its parent cell line CAL27 were transfected with miR-181a mimics and miR-181a LNA respectively. Western blot and immunofluorescence staining were used to detect the expression of E-cadherin and Vimentin; Western blot was used to detect the expression of Twist1 and Slug; Transwell assay and scratch test were used to detect the invasion and migration capabilities; MTT was used to analyze the half maximal inhibitory concentration (IC₅₀) values. Bioinformatics analysis was performed and found that Twist1 was directly targeted by miR-181a. Luciferase reporter gene plasmids were constructed and designed obligos including miR-181a targeting site. Dual luciferase reporter gene array was performed. SPSS17.0 software package was used to analyze the results. RESULTS: miR-181a mimics transfection reversed the EMT phenotype of CAL27/CDDP. The expression of E-cadherin was up-regulated and the expression of Vimentin, Twist1 and Slug was down-regulated. The motility was significantly decreased. IC₅₀ of CAL27/CDDP decreased by 47.57%±6.23% (P<0.05). miR-181a LNA transfection induced EMT in CAL27. The expression of E-cadherin was down-regulated and the expression of Vimentin, Twist1 and Slug was up-regulated. The motility was significantly increased. IC₅₀ of CAL27 increased by 55.61%±7.20%(P<0.05).CONCLUSIONS: MiR-181a inhibits EMT and CDDP drug-resistance by directly targeting Twist1 in TSCC.

Key words: Tongue squamous cell carcinoma, Epithelial-mesenchymal transition, microRNA, Twist1, Drug resistance