三氧化二砷通过抑制 RPL22L1 调节糖酵解途径治疗急性早幼粒细胞白血病。
Arsenic trioxide regulates the glycolytic pathway to treat acute promyelocytic leukemia by inhibiting RPL22L1.
机构信息
Department of Hematology, the Second Affiliated Hospital of Qiqihar Medical University, China.
Department of Laboratory Medicine, The Second Affiliated Hospital of Qiqihar Medical University, China.
出版信息
Leuk Res. 2024 Sep;144:107550. doi: 10.1016/j.leukres.2024.107550. Epub 2024 Jul 24.
OBJECTIVE
To investigate the relationship between the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO) and glycolysis, as well as its underlying molecular mechanism.
METHODS
The GEO database was used to analyze alterations in the expression of RPL22L1 in APL patients and its correlation with glycolysis. The levels of RPL22L1 and glycolysis were assessed in 9 paired clinical samples. NB4 cells and NB4 cells with knockdown of RPL22L1 were treated with ATO. The protein and mRNA of RPL22L1 were detected using RT-PCR and Western blot, and the content was determined by using glucose, pyruvate, and lactate detection kits. Finally, detection of cell proliferation using CCK8, migration by scratch assay, and apoptosis by flow cytometry, and the biological function of ATO in NB4 cells was examined.
RESULTS
The expression of RPL22L1 in GSE213742 and GSE234103 datasets exhibited a significant increase in human APL cells, specifically NB4 cells. RPL22L1 in GSE213742 and GSE234103 gene expression matrix was significantly elevated in human APL cells NB4 cells, and further analysis found RPL22L1 showed a strong positive correlation with glycolysis. Cellular experiments showed that ATO inhibited RPL22L1 in NB4 cells and inhibited glycolysis in APL cells. The ATO played a pivotal role in suppressing the proliferation, migration, as well as invasion of NH4 cells.
CONCLUSION
ATO regulates the blycolytic pathway in APL by inhibiting RPL22L1 expression, and this may contribute to its therapeutic effects.
目的
探讨三氧化二砷（ATO）治疗急性早幼粒细胞白血病（APL）与糖酵解的关系及其潜在的分子机制。
方法
利用 GEO 数据库分析 APL 患者中 RPL22L1 表达的改变及其与糖酵解的相关性。评估 9 对临床样本中 RPL22L1 的水平和糖酵解水平。用 ATO 处理 NB4 细胞和敲低 RPL22L1 的 NB4 细胞。采用 RT-PCR 和 Western blot 检测 RPL22L1 的蛋白和 mRNA，使用葡萄糖、丙酮酸和乳酸检测试剂盒测定含量。最后，用 CCK8 检测细胞增殖，划痕实验检测迁移，流式细胞术检测凋亡，检测 ATO 在 NB4 细胞中的生物学功能。
结果
在 GSE213742 和 GSE234103 数据集的 RPL22L1 表达在人 APL 细胞，特别是 NB4 细胞中显著增加。在 GSE213742 和 GSE234103 基因表达矩阵中，RPL22L1 在人 APL 细胞 NB4 细胞中显著升高，进一步分析发现 RPL22L1 与糖酵解呈强正相关。细胞实验表明 ATO 抑制 NB4 细胞中的 RPL22L1，并抑制 APL 细胞中的糖酵解。ATO 在抑制 NH4 细胞的增殖、迁移和侵袭中起关键作用。
结论
ATO 通过抑制 RPL22L1 的表达调节 APL 中的糖酵解途径，这可能有助于其治疗效果。
Zotero 插件