SPAG6-silencing enhances decitabine-induced apoptosis and demethylation of PTEN in SKM-1 cells and in a xenograft mouse model. Issue 9 (29th July 2021)

• Record Type: Journal Article
• Authors: Luo, Jie; Mu, Jiao; Zhang, Meng; Zhao, Beibei; Liu, Lin
• Is Part Of: Leukemia & lymphoma. Volume 62:Issue 9(2021)
• Page Start: 2242
• Page End: 2252
• Publication Date: 2021-07-29
• Subjects: Myelodysplastic syndromes -- sperm-associated antigen 6 -- PTEN -- methylation -- apoptosis; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2021.1913148
• Languages: English
• ISSNs: 1042-8194

Abstract

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.