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Oncotarget ; 6(1): 258-70, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25404641

RESUMO

Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin in the metastasis of human chondrosarcoma is largely unknown. Here, we found that the expression of resistin was higher in chondrosarcoma biopsy tissues than in normal cartilage. Moreover, treatment with resistin increased matrix metalloproteinase (MMP)-2 expression and promoted cell migration in human chondrosarcoma cells. Co-transfection with microRNA (miR)-519d mimic resulted in reversed resistin-mediated cell migration and MMP-2 expression. Additionally, AMP-activated protein kinase (AMPK) and p38 inhibitors or siRNAs reduced the resistin-increased cell migration and miR-519d suppression, and inhibition of resistin expression resulted in suppression of MMP-2 expression and lung metastasis in vivo. Taken together, our results indicate that resistin promotes chondrosarcoma metastasis and MMP-2 expression through activation of the AMPK/p38 signaling pathway and down-regulation of miR-519d expression. Therefore, resistin may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias Ósseas/metabolismo , Condrossarcoma/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/metabolismo , Resistina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Movimento Celular , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos SCID , Metástase Neoplásica , Transplante de Neoplasias , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
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