DNMTs-mediated SOCS3 methylation promotes the occurrence and development of AML.
Eur J Haematol
; 112(3): 439-449, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-37950514
ABSTRACT
OBJECTIVES:
As a tumor suppressor gene, SOCS3 inhibits the growth of tumor cells by regulating JAK/STAT signaling pathway through negative feedback. This study aimed to investigate the biological function and mechanism of SOCS3 methylation mediated by DNMTs in the development of AML.METHODS:
Bone marrow samples were collected from 70 AML patients and 20 healthy volunteers. The expression and methylation status of each gene were detected by RT-qPCR, western blot and MS-PCR, and the growth and apoptosis rate of leukemia cell lines were detected by CCK-8 and flow cytometry. The effects of changes in SOCS3 gene expression and methylation status of AML cell lines were observed by gene transfection and gene knockdown.RESULTS:
The methylation rate of SOCS3 in AML initial treatment group was significantly higher than that in the remission group and the normal control group (60% vs. 0%, 0%). The expression of SOCS3 in the SOCS3 methylation group was significantly lower than that in the non-methylated group and control group, while the expression of DNMT1, DNMT3a, p-JAK2, p-STAT3 and p-STAT5 were significantly higher than those in the non-methylated group and control group. Demethylation treatment, SOCS3 transfection and DNMT3a knockdown could up-regulate the expression of SOCS3, which decreased the proliferation and increased the apoptosis of leukemia cell lines.CONCLUSION:
SOCS3 methylation mediated by DNMTs promotes the occurrence and development of AML and can be used as a potential biomarker for the diagnosis and efficacy evaluation of AML.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Transducción de Señal
Límite:
Humans
Idioma:
En
Revista:
Eur J Haematol
Asunto de la revista:
HEMATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China