The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis.
Lab Invest
; 97(8): 946-961, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28504687
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At present, there is no well-established targeted drug for majority of patients. The kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and is dysregulated in multiple cancers. The objectives of this study were to evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate its biological functions in MB pathogenesis. By quantitative RT-PCR and immunohistochemistry, we found KIF14 was overexpressed in MB. Increased KIF14 expression at protein level was strongly associated with shorter progression-free survival (P=0.0063) and overall survival (P=0.0083). Fluorescence in situ hybridization (FISH) analysis confirmed genomic gain of chromosome 1q in 17/93 (18.3%) of MB. Combined genetic and immunohistochemical analyses revealed that 76.5% of MB with 1q gain showed consistent overexpression of KIF14, and a tight link between chromosome 1q gain and KIF14 overexpression (P=0.03). Transient, siRNAs-mediated downregulation of KIF14 suppressed cell proliferation and induced apoptosis in two MB cell lines. Stably KIF14 knockdown by shRNAs inhibited cell viability, colony formation, migration and invasion, and tumor sphere formation in MB cells. We conclude that KIF14 is dysregulated in MB and is an adverse prognostic factor for survival. Furthermore, KIF14 is part of MB biology and is a potential therapeutic target for MB.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
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Cinesinas
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Apoptose
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Proteínas Oncogênicas
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Meduloblastoma
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article