Generally, decreased zinc in the serum of tumor patients but increased zinc in tumor cells can be observed. However, the role of zinc homeostasis in myeloid leukemia remains elusive. is essential for the initiation, maintenance, and progression of chronic myelocytic leukemia (CML). We are currently investigating the association between zinc homeostasis and CML. Genes involved in zinc homeostasis were examined using three GEO datasets. Western blotting and qPCR were used to investigate the effects of zinc depletion on expression. Furthermore, the effect of TPEN on promoter activity was determined using the dual-luciferase reporter assay. MRNA stability and protein stability of were assessed using actinomycin D and cycloheximide. Transcriptome data mining revealed that zinc homeostasis-related genes were associated with CML progression and drug resistance. Several zinc homeostasis genes were affected by TPEN. Additionally, we found that zinc depletion by TPEN decreased mRNA stability and transcriptional activity in K562 CML cells. Zinc supplementation and sodium nitroprusside treatment reversed downregulation by TPEN, suggesting zinc- and nitric oxide-dependent mechanisms. Our in vitro findings may help to understand the role of zinc homeostasis in regulation and thus highlight the importance of zinc homeostasis in CML.

中文翻译：

---

锌作为慢性粒细胞白血病细胞 BCR-ABL 癌基因的潜在调节剂

一般来说，肿瘤患者血清中的锌含量减少，但肿瘤细胞中的锌含量增加。然而，锌稳态在骨髓性白血病中的作用仍然难以捉摸。对于慢性粒细胞白血病 (CML) 的发生、维持和进展至关重要。我们目前正在研究锌稳态与 CML 之间的关联。使用三个 GEO 数据集检查了参与锌稳态的基因。使用蛋白质印迹和 qPCR 来研究锌耗尽对表达的影响。此外，使用双荧光素酶报告基因测定法确定了 TPEN 对启动子活性的影响。使用放线菌素 D 和放线菌酮评估 mRNA 稳定性和蛋白质稳定性。转录组数据挖掘表明，锌稳态相关基因与 CML 进展和耐药性相关。一些锌稳态基因受到 TPEN 的影响。此外，我们发现 TPEN 消耗锌会降低 K562 CML 细胞中 mRNA 的稳定性和转录活性。补充锌和硝普钠治疗可逆转 TPEN 的下调，表明锌和一氧化氮依赖性机制。我们的体外研究结果可能有助于了解锌稳态在调节中的作用，从而强调锌稳态在 CML 中的重要性。