Association between methylation of tumor suppressor gene SOCS1 and acute myeloid leukemia.
Oncol Rep
; 40(2): 1008-1016, 2018 Aug.
Article
en En
| MEDLINE
| ID: mdl-29916533
ABSTRACT
Suppressor of cytokine signaling1 (SOCS1) is a widely recognized tumor suppressor gene. Silencing of SOCS1 expression as a result of promoter methylation is associated with occurrence and development of solid tumors such as liver, cervical and pancreatic cancer. However, the association between SOCS1 gene methylation and acute myeloid leukemia (AML) has not been well explored. In the present study, we examined whether gene expression and methylation status of SOCS1 was altered in AML, and whether this was related to disease occurrence and development. To assess this hypothesis, we analyzed SOCS1 in four groups of AML patients i) Initial treatment group (IT); ii) relapsed/refractory group (RR); iii) remission group (RE); and iv) normal control group (NC). We also used leukemia cell lines U937 and THP1 to study the underlying molecular mechanism of SOCS1 in AML, mainly the JAK2/STAT pathway. We used several techniques such as quantitative PCR (qPCR), methylationspecific PCR (MSPCR), western blotting, flow cytometry and cell transfection techniques to analyze the expression and methylation status of SOCS1. We found that the SOCS1 gene methylation rate in the IT and RR groups was significantly higher than that in the RR and NC groups (48, 80 vs. 0 and 0%, respectively). Furthermore, mRNA and protein expression was significantly lower in the IT and RR groups when compared to the RE and NC groups. We also found that the JAK2/STAT signaling pathway was negatively affected by SOCS1. SOCS1 gene methylation caused gene silencing of SOCS1 which overcame the suppression of the downstream JAK2/STAT signaling pathway by SOCS1, and promoted the growth and proliferation of AML cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Leucemia Mieloide Aguda
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Genes Supresores de Tumor
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Metilación de ADN
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Proteína 1 Supresora de la Señalización de Citocinas
Tipo de estudio:
Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2018
Tipo del documento:
Article