TRIM58 suppresses the tumor growth in gastric cancer by inactivation of ß-catenin signaling via ubiquitination.
Cancer Biol Ther
; 21(3): 203-212, 2020.
Article
en En
| MEDLINE
| ID: mdl-31747856
ABSTRACT
Objective:
To investigate and define the underlying molecular mechanism of tripartite motif-containing 58 (TRIM58) in regulating the tumor growth of gastric cancer (GC).Methods:
TRIM58 expression in GC tissues and cells was detected by real-time PCR and Western blot, followed by lentiviral-induced overexpression or knockdown of TRIM58. Subsequently, CCK8, BrdU-ELISA, flow cytometry, immunoprecipitation, in vitro animal experiments and immunochemistry were performed to explore the function of TRIM58. Western blotting was used to detect ß-catenin, C-myc, Cyclin D1, and survivin expression.Results:
TRIM58 expression was significantly reduced in tumor tissues of GC patients and GC cell lines, whereas ß-catenin, C-myc, Cyclin D1, and survivin were highly expressed. Overexpression of TRIM58 in GC cells resulted in decreases in ß-catenin, C-myc, Cyclin D1, and survivin protein expression and significantly suppressed proliferation by preventing cell-cycle progression and promoting cell apoptosis. Conversely, TRIM58 knockdown resulted in the opposite effects. Furthermore, the effect of TRIM58 knockdown on GC cells was potently reversed by a ß-catenin inhibitor, XAV939. Immunoprecipitations showed the interaction between TRIM58 and ß-catenin, and TRIM58 overexpression significantly enhanced ß-catenin degradation. In addition, we found a significant decrease in the growth and weight of tumors and an increase in tumor cell apoptosis in TRIM58-overexpression nude mice, which were also accompanied by reduced ß-catenin expression.Conclusions:
These data suggest that TRIM58 may function as a tumor suppressor in GC and potentially suppress the tumor growth of gastric cancer by inactivation of ß-catenin signaling via ubiquitination.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Biomarcadores de Tumor
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Regulación Neoplásica de la Expresión Génica
/
Ubiquitina
/
Beta Catenina
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Ubiquitinación
/
Proteínas de Motivos Tripartitos
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Animals
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Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer Biol Ther
Asunto de la revista:
NEOPLASIAS
/
TERAPEUTICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China