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Biomed Pharmacother ; 107: 689-695, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30130730

RESUMO

CXC chemokine ligand 9, a member of "cytokine milieu", makes up the microenvironment of lymphoma and plays an important role in the occurrence and development of lymphoma. However, the role of CXC chemokine ligand 9 and its underlying mechanism remains largely unknown in the progression of diffuse large B-cell lymphoma. Wnt/ ß -catenin signaling is reported to play an important role in diffuse large B-cell lymphoma, and the overexpression and nuclear accentuation of ß-catenin in diffuse large B-cell lymphoma patients' tissues were closely associated with the advanced clinical staging. The present study aimed to explore the effects of CXC chemokine ligand 9 on the progression of diffuse large B-cell lymphoma and determine if ß -catenin is involved in this process. We firstly detected the expression pattern of CXC chemokine ligand 9 in diffuse large B-cell lymphoma tissues and cell lines, and determined the relationship between CXC chemokine ligand 9 expression level and patients' progression and prognosis. Then we used the loss/gain of function approach to determine the effects of CXC chemokine ligand 9 on cell viability, apoptosis and migration. Finally, we assessed the expression and subcellular location of ß-catenin after CXC chemokine ligand 9 up/down-regulation by Western Blot. Our results showed that CXC chemokine ligand 9 was highly expressed in diffuse large B-cell lymphoma tissues and cell lines, which showed close association with patients' advanced clinical progression and shorter overall survival. Up-regulation of CXC chemokine ligand 9 promoted the viability and migration and repressed the apoptosis of OCI-Ly8 cells, as well as increased ß-catenin expression and translocated it from cytoplasm to nuclear, while these effects were abolished when knockdown ß-catenin. In conclusion, this work reveals that CXC chemokine ligand 9 promotes the progression of diffuse large B-cell lymphoma in a ß-catenin-dependent manner. Our study provides evidence for the mechanism by which CXC chemokine ligand 9 may function as an oncogene and the potential of serving CXC chemokine ligand 9 as a therapeutic target for diffuse large B-cell lymphoma.


Assuntos
Quimiocina CXCL9/metabolismo , Progressão da Doença , Linfoma Difuso de Grandes Células B/patologia , Regulação para Cima/genética , beta Catenina/genética , Adulto , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/metabolismo , Sobrevivência Celular/genética , Quimiocina CXCL9/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Prognóstico
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