Knockdown of TRIM24 suppresses growth and induces apoptosis in acute myeloid leukemia through downregulation of Wnt/GSK-3ß/ß-catenin signaling.
Hum Exp Toxicol
; 39(12): 1725-1736, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32672070
ABSTRACT
Tripartite motif-containing protein 24 (TRIM24) has currently emerged as a crucial cancer-related gene present in a wide range of human cancer types. However, the involvement of TRIM24 in acute myeloid leukemia (AML) has not been well investigated. The present study aims to investigate the significance, cellular function, and potential regulatory mechanism of TRIM24 in AML. We found that TRIM24 expression was significantly upregulated in AML compared with normal tissues. AML patients with low expression of TRIM24 had higher survival rates than those expressing TRIM24 at higher levels. High expression of TRIM24 was also detected in AML cells and its knockdown markedly restricted proliferation and promoted apoptosis in AML cells. Further investigation revealed that TRIM24 contributed to the regulation of Wnt/ß-catenin signaling, which was associated with modulating the phosphorylation status of glycogen synthase kinase-3ß (GSK-3ß). Inactivation of GSK-3ß partially reversed the TRIM24 knockdown-mediated antitumor effects observed in AML cells. Furthermore, knockdown of TRIM24 retarded the growth of AML-derived xenograft tumors in nude mice in vivo. Overall, these findings demonstrate that knockdown of TRIM24 impedes the AML tumor growth through the modulation of Wnt/GSK-3ß/ß-catenin signaling. These findings highlight the potential TRIM24 as an attractive anticancer target to treat AML.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_leukemia
Asunto principal:
Leucemia Mieloide Aguda
/
Proteínas Portadoras
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Exp Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China