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 χ 2 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 on p21, p53  and Cyclin D1  expression and EMT process.
Conclusion: These results indicated that MBD2  confers 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.
Keywords: MBD2, RCC, prognosis