FLI-1 mediates tumor suppressor function via Klotho signaling in regulating CRC.
Cell Biol Int
; 44(7): 1514-1522, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32196848
ABSTRACT
Colorectal cancer (CRC) is an aggressive malignancy with a high incidence and mortality rate. Although a targeting therapy has been developed, the 5-year survival rate is still very low in CRC patients with distant metastasis. Thus, the identification of new targets is still significant for improving CRC treatment. Klotho is a tumor suppressor, and its expression is aberrant in CRC. In this study, the roles of the FLI-1 gene in regulating Klotho gene expression and Klotho-associated signaling, as well as the effects of FLI-1 on colony formation, invasion, and apoptosis were investigated in CRC cell lines. The methylation of the FLI-1 gene was analyzed using a commercial methylation kit. Results showed that FLI-1 messenger RNA and protein expression were downregulated in six CRC cell lines when compared with the normal colon mucosal epithelial cell line, which negatively correlated with the level of DNA methylation. Silencing of FLI-1 gene expression decreased Klotho protein expression and phosphorylation of ß-catenin protein at Thr41 /Ser45 , but increased Wnt3a and ß-catenin protein expression and IGF-1R phosphorylation in HT29 cells. In contrast to silencing FLI-1, overexpressing FLI-1 significantly increased Klotho protein expression and phosphorylation of ß-catenin protein at Thr41 /Ser45 , but decreased Wnt3a and ß-catenin protein expression and IGF-1R phosphorylation in Caco-2 cells. Silencing of FLI-1 gene expression significantly increased colony formation and invasion, but decreased apoptosis in HT29 cells. In contrast, overexpressing the FLI-1 gene significantly decreased colony formation and invasion, but increased apoptosis in Caco-2 cells. These findings suggest that FLI-1 functions as a tumor suppressor in CRC cells and positively regulates Klotho signaling. Hypermethylation may be one of the causes of the loss of FLI-1 gene expression in CRC cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Regulação Neoplásica da Expressão Gênica
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Proteína Proto-Oncogênica c-fli-1
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Glucuronidase
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Biol Int
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China