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

Autor(es):Mostrar menos -

Valente, Valeria ^{[1, 2]} ; Serafim, Rodolfo Bortolozo ^[1] ; de Oliveira, Leonardo Cesar ^[1] ; Adorni, Fernando Soares ^[1] ; Torrieri, Raul ^[3] ; da Cunha Tirapelli, Daniela Pretti ^[4] ; Espreafico, Enilza Maria ^[5] ; Oba-Shinjo, Sueli Mieko ^[6] ; Nagahashi Marie, Suely Kazue ^[6] ; Paco-Larson, Maria Luisa ^[5] ; Carlotti, Jr., Carlos Gilberto ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara - Brazil

^[2] NAP USP, Ctr Integrat Syst Biol CISBi, Ribeirao Preto - Brazil

^[3] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol, Ribeirao Preto - Brazil

^[6] Univ Sao Paulo, Fac Med, Dept Neurol, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 4 APR 25 2013.
• Citações Web of Science: 19

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. (AU)

• Processo FAPESP: 06/57602-9 - Análise de genes diferencialmente expressos em glioblastoma: busca de marcadores para diagnóstico e investigação de aspectos moleculares da biologia tumoral
• Beneficiário: Valeria Valente
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
• Beneficiário: Suely Kazue Nagahashi Marie
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/05674-4 - Análise dos efeitos do silenciamento de HJURP(Holliday Junction-Recognizing protein) em linhagens celulares de glioblastoma multiforme
• Beneficiário: Fernando Soares Adorni
• Linha de fomento: Bolsas no Brasil - Iniciação Científica