SPAG6-silencing enhances decitabine-induced apoptosis and demethylation of PTEN in SKM-1 cells and in a xenograft mouse model.

Myelodysplastic syndromes (MDS) are a group of malignant diseases that are characterized by disordered hematopoiesis with a high risk of transforming into leukemia. In the present study, SPAG6-knockdown and decitabine (DAC) treatment resulted in a decreased DNA methyltransferases and methyl-CpG-binding domain protein expression. In addition, DAC and LBH589 were shown to promote apoptosis in SKM-1 cells, and SPAG6-knockdown to enhance the pro-apoptotic effect of DAC. DAC could reduce PTEN methylation and increase PTEN expression in SKM-1 cells. SPAG6-knockdown and LBH589 treatment could increase DAC-mediated demethylation of PTEN promoter. Finally, a mouse model was constructed, and an enhanced efficacy of DAC following SPAG6-knockdown was confirmed . In conclusion, DAC-mediated apoptosis and PTEN promoter demethylation may be synergistically enhanced by SPAG6-silencing. Therefore, in the present study it was indicated that SPAG6 may be a potential target for demethylation therapy in MDS.