MicroRNA 520d-3p inhibits gastric cancer cell proliferation, migration, and invasion by downregulating EphA2 expression.
Mol Cell Biochem
; 396(1-2): 295-305, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25063221
ABSTRACT
Aberrant expression of microRNAs (miRNAs) has been shown to play important roles in cancer progression as a result of changes in expression of their target genes. In this study, we investigated the roles of miR-520d-3p on gastric cancer (GC) cell proliferation, migration, and invasion, and confirmed that this miRNA regulates EphA2 expression. The mRNA expression levels of miR-520d-3p and EphA2 in GC tissues and cell lines were evaluated. The clinical and prognostic significance of miR-520d-3p was assessed. The biological function of miR-520d-3p in GC cells was investigated using a methylthiazolyldiphenyl-tetrazolium bromide assay, cell cycle assay, transwell invasion assay, and wound-healing assay. miR-520d-3p expression was down-regulated and inversely correlated with the expression of EphA2 in GC tissues and cell lines. Lower expression of miR-520d-3p was associated with tumor invasion (P = 0.0357), lymph nodes metastasis (P = 0.0272), a higher clinical stage (P = 0.0041), and poorer overall survival (P = 0.0105). Luciferase assays revealed that miR-520d-3p inhibited EphA2 expression by targeting the 3'-untranslated region of EphA2 mRNA. Overexpression of miR-520d-3p dramatically inhibited the proliferation, cell cycle progression, invasion, and migration of GC cells, while down-regulation substantially promoted these properties. Moreover, c-Myc, CyclinD1, and matrix metalloproteinase-9 expression levels were down-regulated in miR-520d-3p mimic-transfected cells and up-regulated in miR-520d-3p inhibitor-transfected cells. Taken together, our data showed that miR-520d-3p appears to contribute to GC progression via the regulation of EphA2 and could serve as a novel prognostic and potential therapeutic marker.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Receptor EphA2
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MicroRNAs
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2014
Tipo de documento:
Article