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Br J Cancer ; 111(10): 2003-13, 2014 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-25211657

RESUMO

BACKGROUND: Dysregulated microRNAs (miRNAs) can serve as oncogenes or suppressors and are associated with many cancers, including oesophageal squamous cell carcinoma (ESCC). METHODS: An alignment miRNA array was used to identify differentially expressed miRNAs in ESCC tissues. The expression of miR-183 and programmed cell death 4 (PDCD4) in oesophageal tissues from ESCC and early oesophageal carcinoma patients was examined by quantitative reverse transcriptase PCR and western blotting. A luciferase assay was performed to confirm miR-183 target genes. The effects of miR-183 on ESCC cells and the associated mechanisms were established by in vitro experiments. RESULTS: We identified 51 upregulated miRNAs and 17 downregulated miRNAs in our array, and miR-183 was one of the most upregulated miRNAs. An inverse correlation between miR-183 and PDCD4 levels was found in ESCC tissues. Upregulated expression of miR-183 was not correlated with tumour stage or lymphatic metastasis in ESCC patients. The luciferase assay confirmed that miR-183 directly interacted with the PDCD4 mRNA 3'-untranslated region in ESCC cells. Overexpression of miR-183 led to decreased PDCD4 protein levels and promoted ESCC cell proliferation and invasion. Inhibition of the PI3K/Akt signalling pathway increased PDCD4 protein levels and decreased miR-183 expression in ESCC cells. CONCLUSIONS: MiR-183 promotes ESCC cell proliferation and invasion by directly targeting PDCD4, which suggests that it is involved in the pathogenesis of ESCC.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/secundário , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas de Ligação a RNA/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Sequência de Bases , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Adesão Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Esôfago/metabolismo , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Dados de Sequência Molecular , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Células Tumorais Cultivadas
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