Arsenic trioxide regulates the glycolytic pathway to treat acute promyelocytic leukemia by inhibiting RPL22L1

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research Pub Date : 2024-07-24 DOI:10.1016/j.leukres.2024.107550

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引用次数: 0

Abstract

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.

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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

目的研究三氧化二砷（ATO）治疗急性早幼粒细胞白血病（APL）与糖酵解之间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 的表达变化及其与糖酵解的相关性。在9个配对临床样本中评估了RPL22L1和糖酵解的水平。用ATO处理NB4细胞和敲除RPL22L1的NB4细胞。使用 RT-PCR 和 Western 印迹检测 RPL22L1 的蛋白和 mRNA，并使用葡萄糖、丙酮酸和乳酸检测试剂盒测定其含量。结果在 GSE213742 和 GSE234103 数据集中，RPL22L1 的表达在人 APL 细胞，特别是 NB4 细胞中显著增加。GSE213742 和 GSE234103 基因表达矩阵中的 RPL22L1 在人 APL 细胞 NB4 细胞中明显升高，进一步分析发现 RPL22L1 与糖酵解呈强正相关。细胞实验表明，ATO抑制了NB4细胞中的RPL22L1，并抑制了APL细胞中的糖酵解。结论ATO通过抑制RPL22L1的表达来调节APL的糖酵解途径，这可能是其治疗效果的原因之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Leukemia research 医学-血液学

CiteScore

4.00

自引率

3.70%

发文量

259

审稿时长

1 months

期刊介绍： Leukemia Research an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. The editors encourage the submission of articles relevant to hematological malignancies. The Journal scope includes reporting studies of cellular and molecular biology, genetics, immunology, epidemiology, clinical evaluation, and therapy of these diseases.