Inhibition of miR194 suppresses the Wnt/ßcatenin signalling pathway in gastric cancer.
Oncol Rep
; 40(6): 3323-3334, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30542715
ABSTRACT
A mounting body of evidence has revealed that microRNAs (miRs) serve pivotal roles in various developmental processes, and in tumourigenesis, by binding to target genes and subsequently regulating gene expression. Continued activation of the Wnt/ßcatenin signalling is positively associated with human malignancy. In addition, miR194 dysregulation has been implicated in gastric cancer (GC); however, the molecular mechanisms underlying the effects of miR194 on GC carcinogenesis remain to be elucidated. The present study demonstrated that miR194 was upregulated in GC tissues and SUFU negative regulator of Ηedgehog signaling (SUFU) was downregulated in GC cell lines. Subsequently, inhibition of miR194 attenuated nuclear accumulation of ßcatenin, which consequently blocked Wnt/ßcatenin signalling. In addition, the cytoplasmic translocation of ßcatenin induced by miR194 inhibition was mediated by SUFU. Furthermore, genes associated with the Wnt/ßcatenin signalling pathway were revealed to be downregulated following inhibition of the Wnt signalling pathway by miR194 suppression. Finally, the results indicated that cell apoptosis was markedly increased in response to miR194 inhibition, strongly suggesting the carcinogenic effects of miR194 in GC. Taken together, these findings demonstrated that miR194 may promote gastric carcinogenesis through activation of the Wnt/ßcatenin signalling pathway, making it a potential therapeutic target for GC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Neoplasias Gástricas
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Regulação Neoplásica da Expressão Gênica
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MicroRNAs
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Via de Sinalização Wnt
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article