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Mol Cell Biochem ; 388(1-2): 39-49, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24242138

RESUMEN

Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR-141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , MicroARNs/genética , Neoplasias Pancreáticas/genética , Fosfoproteínas/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Apoptosis/genética , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Caspasa 3 , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Páncreas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Interferencia de ARN , ARN Interferente Pequeño , Factores de Transcripción , Proteínas Señalizadoras YAP
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