Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Leuk Lymphoma. 2021 Sep;62(9):2242-2252. doi: 10.1080/10428194.2021.1913148. Epub 2021 Apr 10.
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.
骨髓增生异常综合征（MDS）是一组恶性疾病，其特征为造血紊乱，有向白血病转化的高风险。在本研究中，敲低 SPAG6 和地西他滨（DAC）处理导致 DNA 甲基转移酶和甲基-CpG 结合域蛋白表达降低。此外，DAC 和 LBH589 促进 SKM-1 细胞凋亡，而敲低 SPAG6 增强 DAC 的促凋亡作用。DAC 可降低 SKM-1 细胞中 PTEN 的甲基化并增加其表达。敲低 SPAG6 和 LBH589 处理可增加 DAC 介导的 PTEN 启动子去甲基化。最后构建了一个小鼠模型，并证实敲低 SPAG6 后 DAC 的疗效增强。总之，DAC 介导的凋亡和 PTEN 启动子去甲基化可能通过沉默 SPAG6 协同增强。因此，本研究表明 SPAG6 可能是 MDS 去甲基化治疗的潜在靶点。
