title: Modulation of HJURP (Holliday Junction-Recognizing Protein) levels is correlated with glioblastoma cells survival.
abstract: 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.
  
  
  RESULTS
  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.
authors: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, University of São Paulo State (UNESP), Araraquara, Brazil. valenteval@gmail.com
authors: Valeria
authors: V
authors: Valente
authors: Rodolfo Bortolozo
authors: RB
authors: Serafim
authors: Leonardo Cesar
authors: LC
authors: de Oliveira
authors: Fernando Soares
authors: FS
authors: Adorni
authors: Raul
authors: R
authors: Torrieri
authors: Daniela Pretti da Cunha
authors: DP
authors: Tirapelli
authors: Enilza Maria
authors: EM
authors: Espreafico
authors: Sueli Mieko
authors: SM
authors: Oba-Shinjo
authors: Suely Kazue Nagahashi
authors: SK
authors: Marie
authors: Maria Luisa
authors: ML
authors: Paçó-Larson
authors: Carlos Gilberto
authors: CG
authors: Carlotti
mesh_terms: D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C524371:HJURP protein, human
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