Zinc as a potential regulator of the BCR-ABL oncogene in chronic myelocytic leukemia cells.
BCR-ABL
Chronic myelogenous leukemia
Nitric oxide
Sodium nitroprusside
TPEN
Zinc homeostasis
Journal
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
ISSN: 1878-3252
Titre abrégé: J Trace Elem Med Biol
Pays: Germany
ID NLM: 9508274
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
received:
29
11
2023
revised:
21
01
2024
accepted:
30
01
2024
medline:
18
3
2024
pubmed:
8
2
2024
entrez:
7
2
2024
Statut:
ppublish
Résumé
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. BCR-ABL 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 BCR-ABL expression. Furthermore, the effect of TPEN on BCR-ABL promoter activity was determined using the dual-luciferase reporter assay. MRNA stability and protein stability of BCR-ABL 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 BCR-ABL mRNA stability and transcriptional activity in K562 CML cells. Zinc supplementation and sodium nitroprusside treatment reversed BCR-ABL downregulation by TPEN, suggesting zinc- and nitric oxide-dependent mechanisms. Our in vitro findings may help to understand the role of zinc homeostasis in BCR-ABL regulation and thus highlight the importance of zinc homeostasis in CML.
Sections du résumé
BACKGROUND
BACKGROUND
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. BCR-ABL is essential for the initiation, maintenance, and progression of chronic myelocytic leukemia (CML). We are currently investigating the association between zinc homeostasis and CML.
METHODS
METHODS
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 BCR-ABL expression. Furthermore, the effect of TPEN on BCR-ABL promoter activity was determined using the dual-luciferase reporter assay. MRNA stability and protein stability of BCR-ABL were assessed using actinomycin D and cycloheximide.
RESULTS
RESULTS
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 BCR-ABL mRNA stability and transcriptional activity in K562 CML cells. Zinc supplementation and sodium nitroprusside treatment reversed BCR-ABL downregulation by TPEN, suggesting zinc- and nitric oxide-dependent mechanisms.
CONCLUSION
CONCLUSIONS
Our in vitro findings may help to understand the role of zinc homeostasis in BCR-ABL regulation and thus highlight the importance of zinc homeostasis in CML.
Identifiants
pubmed: 38325182
pii: S0946-672X(24)00027-0
doi: 10.1016/j.jtemb.2024.127407
pii:
doi:
Substances chimiques
Fusion Proteins, bcr-abl
EC 2.7.10.2
Zinc
J41CSQ7QDS
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
R9PTU1U29I
Ethylenediamines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127407Informations de copyright
Copyright © 2024 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.