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Made available in DSpace on 2014-12-03T13:11:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-04-25Bitstream added on 2014-12-03T13:22:30Z : No. of bitstreams: 1 WOS000318341400043.pdf: 5076716 bytes, checksum: 9511b533bf166bce399ed953ca17e01b (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundacao de Apoio ao Ensino, Pesquisa e Assistencia (FAEPA) do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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. Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil NAP USP, Ctr Integrat Syst Biol CISBi, Ribeirao Preto, Brazil Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, Ribeirao Preto, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol, Ribeirao Preto, Brazil Univ Sao Paulo, Fac Med, Dept Neurol, Ribeirao Preto, Brazil Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil FAPESP: 04/12133-6 FAPESP: 06/57602-9 FAPESP: 11/05674-4 CNPq: 485342/2006-5 CNPq: 154707/2006-6 CNPq: 19347/2011