Abstract
PURPOSE: DNA methylation plays an important role in regulating gene expression. Methyl-CpG-binding domain (MBD) proteins recognize and bind to methylated DNA, which mediate gene silencing by the interaction with deacetylases and histone methyltransferases. MBD2 has been reported in various human cancers; however, its clinical implication and potential regulatory role in renal cell carcinoma (RCC) have not been elaborated. MATERIALS AND METHODS: In the study, we estimated the expression and prognostic value of MBD2 in RCC cell lines and tissues by Western blotting and immunohistochemistry. The associations of MBD2 expression and pathological characters and survival in RCC patients were performed using χ2 and Kaplan-Meier survival analysis, respectively. Univariate and multivariable Cox regression analyses suggested the independent predictors in RCC prognosis. The functional role of MBD2 in RCC progression was assessed by in vitro cell experiments. In addition, we identified the MBD2-mediated alterations of protein-related proliferation and EMT markers in RCC cells after MBD2 overexpression and knockdown. RESULTS: We found that the protein levels of MBD2 were upregulated in RCC cells and tissues. High MBD2 expression was related to TNM stage and predicted poorer survival in RCC. Enforced expression of MBD2 significantly promoted the proliferation, cycle progress, invasion and migration of RCC cells in vitro. However, downregulating MBD2 remarkably weakened the above cell functions. Mechanistically, the promotive effect of MBD2 overexpression may be regulated by its effects onp21, p53 and Cyclin D1 expression and EMT process. CONCLUSION: These results indicated that MBD2confers an oncogenic function in the malignant progression of RCC. MBD2 could be served as a meaningful prognostic biomarker and a latent therapeutic target in RCC patients.