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Genet Mol Res ; 14(4): 16133-45, 2015 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-26662405

RESUMO

It has been shown that microRNA-215 (miR-215) is dysregulated in several human malignancies, and this correlates with tumor progression. However, its expression and function in pancreatic cancer is still unclear. The aim of this study was to explore the effects of miR-215 on pancreatic cancer formation and progression. Using quantitative RT-PCR, we detected miR-215 expression in pancreatic cancer cell lines and primary tumor tissues. The association of miR-215 expression with clinicopathological factors and prognosis was also analyzed. We then observed the effects of miR-215 on the biological behavior of pancreatic cancer cells. Lastly, the potential regulatory function of miR-215 on ZEB2 expression was investigated. miR-215 expression levels were significantly downregulated in pancreatic cancer samples and cell lines. Decreased miR-215 expression was significantly associated with large tumor size, advanced TNM stage, lymph node metastasis, vessel invasion, and lower overall survival. Multivariate regression analysis corroborated that downregulation of miR-215 was an independent unfavorable prognostic factor. Overexpression of miR-215 inhibited pancreatic cancer cell proliferation, invasion, and migration; promoted cell apoptosis in vitro; and suppressed tumorigenicity in vivo. Further, ZEB2 was confirmed as a direct target of miR-215 by using a luciferase reporter assay. These findings indicate that miR-215 may act as a tumor suppressor in pancreatic cancer cells, and could serve as a novel therapeutic target for miR-based therapy.


Assuntos
Genes Supressores de Tumor , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Interferência de RNA , Proteínas Repressoras/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Apoptose/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Proteínas de Homeodomínio/química , Humanos , Masculino , Camundongos , MicroRNAs/química , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Mensageiro/química , RNA Mensageiro/genética , Proteínas Repressoras/química , Carga Tumoral , Homeobox 2 de Ligação a E-box com Dedos de Zinco
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