Modulation of HJURP (Holliday Junction-Recognizing Protein) Levels Is Correlated with Glioblastoma Cells Survival

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art_VALENTE_Modulation_of_HJURP_(Holliday_Junction_Recognizing_Protein)_Levels_2013.PDF (4.84 MB)
Citações na Scopus
38
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
VALENTE, Valeria
SERAFIM, Rodolfo Bortolozo
OLIVEIRA, Leonardo Cesar de
ADORNI, Fernando Soares
TORRIERI, Raul
TIRAPELLI, Daniela Pretti da Cunha
ESPREAFICO, Enilza Maria
PACO-LARSON, Maria Luisa
Citação
PLOS ONE, v.8, n.4, article ID e62200, 10p, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Diffuse astrocytomas are the most common type of primary brain cancer in adults. They present a wide variation in differentiation and aggressiveness, being classified into three grades: low-grade diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma multiforme (grade IV), the most frequent and the major lethal type. Recent studies have highlighted the molecular heterogeneity of astrocytomas and demonstrated that large-scale analysis of gene expression could help in their classification and treatment. In this context, we previously demonstrated that HJURP, a novel protein involved in the repair of DNA double-strand breaks, is highly overexpressed in glioblastoma. Methodology/Principal Findings: Here we show that HJURP is remarkably overexpressed in a cohort composed of 40 patients with different grade astrocytomas. We also observed that tumors presenting the higher expression levels of HJURP are associated with poor survival prognosis, indicating HJURP overexpression as an independent prognostic factor of death risk for astrocytoma patients. More importantly, we found that HJURP knockdown strongly affects the maintenance of glioblastoma cells in a selective manner. Glioblastoma cells showed remarkable cell cycle arrest and premature senescence that culminated in elevated levels of cell death, differently from non-tumoral cells that were minimally affected. Conclusions: These data suggest that HJURP has an important role in the maintenance of extremely proliferative cells of high-grade gliomas and point to HJURP as a potential therapeutic target for the development of novel treatments for glioma patients.
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URI
https://observatorio.fm.usp.br/handle/OPI/7565
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE
Artigos e Materiais de Revistas Científicas - LIM/15
Artigos e Materiais de Revistas Científicas - ODS/03