Zhou Qingbing, Liang Yuanbin, Chen Ruofan, Wang Hongzhi, Guo Qiuyue, Liu Li, Zhu Xiaobo, Xu Fengqin
Institute of Geriatric Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Sci Rep. 2025 May 29;15(1):18943. doi: 10.1038/s41598-025-01867-6.
DNA methylation plays a critical role in myelodysplastic syndrome (MDS). Here, we aimed to observe the effects of polydatin (PD) on DNA methylation in MDS cells on a genome-wide scale and explore the underlying mechanisms, providing new evidence for PD as a novel hypermethylation agent. We used the Gene Expression Omnibus (GEO) online database to evaluate the DNA methylation characteristics of MDS patients. A Human Methylation 850 K BeadChip was used to evaluate the effects of PD on DNA methylation in SKM-1 cells. Western blotting (WB) was used to observe changes in the expression of related proteins. Cytoscape was used to determine the key genes that were hypermethylated by PD. The therapeutic effects were evaluated using flow cytometry experiment and a cell counting kit-8 (CCK-8) assay in vitro. Data from the GEO online database revealed that aberrant gene hypomethylation plays an important role in MDS. In MDS cells, 448 genes (71.91%) were hypermethylated following PD treatment. These hypermethylated genes are related to cancer-related signaling pathways. Moreover, key hypermethylated genes, including PIK3CA, ITPR3 and SPOPL, were identified, and these three genes are all oncogenes. Most importantly, PD decreased the protein expression of the above three oncogenes. Finally, we found that PD could inhibit the proliferation of MDS cells, arrest them in the S phase and induce their apoptosis. Our findings demonstrated that PD has therapeutic effects on MDS by inhibiting the protein expression of oncogenes via hypermethylation in vitro, indicating that PD may be a novel hypermethylation agent.
DNA甲基化在骨髓增生异常综合征（MDS）中起关键作用。在此，我们旨在在全基因组范围内观察虎杖苷（PD）对MDS细胞中DNA甲基化的影响，并探索其潜在机制，为PD作为一种新型高甲基化剂提供新证据。我们使用基因表达综合数据库（GEO）在线数据库评估MDS患者的DNA甲基化特征。使用人类甲基化850K芯片评估PD对SKM-1细胞中DNA甲基化的影响。采用蛋白质免疫印迹法（WB）观察相关蛋白表达的变化。使用Cytoscape软件确定被PD高甲基化的关键基因。在体外通过流式细胞术实验和细胞计数试剂盒-8（CCK-8）检测评估治疗效果。GEO在线数据库的数据显示，异常基因低甲基化在MDS中起重要作用。在MDS细胞中，PD处理后有448个基因（71.91%）发生高甲基化。这些高甲基化基因与癌症相关信号通路有关。此外，还鉴定出关键的高甲基化基因，包括PIK3CA、ITPR3和SPOPL，这三个基因均为癌基因。最重要的是，PD降低了上述三种癌基因的蛋白表达。最后，我们发现PD可抑制MDS细胞的增殖，使其停滞于S期并诱导其凋亡。我们的研究结果表明，PD在体外通过高甲基化抑制癌基因的蛋白表达从而对MDS具有治疗作用，这表明PD可能是一种新型高甲基化剂。
