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

Abstract

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 vivo. 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.

Keywords:

• Myelodysplastic syndromes
• sperm-associated antigen 6
• PTEN
• methylation
• apoptosis

Acknowledegments

The authors would like to thank the Experimental Research Center of The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) for the site and technical support.

Author contributions

JL designed and performed the study, and wrote the manuscript. JM participated in designing the study and performed the in vivo experiments. MZ provided technical support. BBZ proofread the manuscript. LL conceived of and designed the research, provided financial support, and contributed to the writing and revisions of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by The National Natural Sciences Foundation of China [grant nos., 82070130 and 81570109].