Objectives: The present study investigated the correlation between the expression of DNA methyltransferase (DNMT)1, DNMT3A, and DNMT3B and the proliferation of mucoepidermoid carcinomas (MECs) using the molecular markers Ki-67 and cyclin D1. This study also demonstrates the effects of 5-aza-2-deoxycytidine (5AC) on the MEC tumor cell lines in relation to DNMT1 and DNMT3A expression, and cell-cycle arrest.
Materials and methods: The immunohistochemistry of DNMT1, DNMT3A, DNMT3B, Ki-67, and cyclin D1 was analyzed in 40 samples of MEC and 15 samples of healthy minor salivary glands. The effects of 5AC on DNMT1 and DNMT3B expression in MEC cell lines were analyzed by Western blot, and the effects of 5AC on the cell cycle were analyzed using flow cytometry.
Results: The expression of DNMT1 and DNMT3B was more intense in MECs than in healthy salivary glands. A strong correlation was found between the expression of the DNMTs and the proliferation markers. This correlation was validated In Vitro, where treatment with 5AC reduced the expression of the DNMTs and the percentage of cells at the G2/M phase of the cell cycle.
Conclusion: The expression of DNMT1, DNMT3A, DNMT3B is correlated significantly with the expression of Ki-67 and cyclin D1. The treatment with 5AC reduces DNMT expression and decreases the percentage of cells at the G2/M phase of the cell cycle, while increasing the cells at the G0/G1 phase.
Keywords: 5-azacytidine; DNA methylation; Mucoepidermoid carcinoma; cell cycle.
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.