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
in En
| MEDLINE
| ID: mdl-31747856
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
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Biomarkers, Tumor
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Gene Expression Regulation, Neoplastic
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Ubiquitin
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Beta Catenin
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Ubiquitination
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Tripartite Motif Proteins
Type of study:
Prognostic_studies
Limits:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Cancer Biol Ther
Journal subject:
NEOPLASIAS
/
TERAPEUTICA
Year:
2020
Document type:
Article
Affiliation country:
Country of publication: