MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway.
Cell Cycle
; 17(24): 2790-2801, 2018.
Article
em En
| MEDLINE
| ID: mdl-30526300
ABSTRACT
Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation. Reinforced expression of miR-300 significantly suppressed the migration of BCa cells. We carried out a search of online databases to predict potential targets of miR-300. Further studies determined that miR-300 directly targeted SP1 and suppressed its expression by specifically binding to its 3'-untranslated region. Meanwhile, downregulated MMP9 may be the final effector of BCa cell mobility. Small interference RNAs silencing SP1 phenocopied the effects of miR-300 overexpression, while restoration of SP1 expression partially rescued the inhibition of metastasis induced by miR-300 overexpression in BCa cells. In conclusion, we unveiled a miR-300/SP1/MMP9 pathway in BCa. These findings demonstrate that miR-300 is a promising tumor suppressor in BCa.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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Fator de Transcrição Sp1
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Metaloproteinase 9 da Matriz
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Peptídeos e Proteínas de Sinalização Intercelular
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MicroRNAs
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article