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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorVALENTE, Valeria
dc.contributor.authorSERAFIM, Rodolfo Bortolozo
dc.contributor.authorOLIVEIRA, Leonardo Cesar de
dc.contributor.authorADORNI, Fernando Soares
dc.contributor.authorTORRIERI, Raul
dc.contributor.authorTIRAPELLI, Daniela Pretti da Cunha
dc.contributor.authorESPREAFICO, Enilza Maria
dc.contributor.authorOBA-SHINJO, Sueli Mieko
dc.contributor.authorMARIE, Suely Kazue Nagahashi
dc.contributor.authorPACO-LARSON, Maria Luisa
dc.contributor.authorCARLOTTI JR., Carlos Gilberto
dc.date.accessioned2014-09-30T14:42:32Z
dc.date.available2014-09-30T14:42:32Z
dc.date.issued2013
dc.description.abstractBackground: 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.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2004/12133-6, 2006/57602-9, 2011/05674-4]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [485342/2006-5, 154707/2006-6, 19347/2011]
dc.description.sponsorshipFundacao de Apoio ao Ensino, Pesquisa e Assistencia (FAEPA) do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
dc.description.sponsorshipCAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
dc.identifier.citationPLOS ONE, v.8, n.4, article ID e62200, 10p, 2013
dc.identifier.doi10.1371/journal.pone.0062200
dc.identifier.issn1932-6203
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/7565
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofPlos One
dc.rightsopenAccess
dc.rights.holderCopyright PUBLIC LIBRARY SCIENCE
dc.subject.otherintegrated genomic analysis
dc.subject.othercenp-a
dc.subject.otherbreast-cancer
dc.subject.otherbrain-tumors
dc.subject.othersubtypes
dc.subject.othergliomas
dc.subject.othersensitivity
dc.subject.othermultiforme
dc.subject.othermutations
dc.subject.otheridh1
dc.subject.wosMultidisciplinary Sciences
dc.titleModulation of HJURP (Holliday Junction-Recognizing Protein) Levels Is Correlated with Glioblastoma Cells Survival
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalVALENTE, Valeria:Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil; NAP USP, Ctr Integrat Syst Biol CISBi, Ribeirao Preto, Brazil
hcfmusp.author.externalSERAFIM, Rodolfo Bortolozo:Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil
hcfmusp.author.externalOLIVEIRA, Leonardo Cesar de:Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil
hcfmusp.author.externalADORNI, Fernando Soares:Univ Sao Paulo State UNESP, Fac Pharmaceut Sci Araraquara, Dept Clin Anal, Araraquara, Brazil
hcfmusp.author.externalTORRIERI, Raul:Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, Brazil
hcfmusp.author.externalTIRAPELLI, Daniela Pretti da Cunha:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, Ribeirao Preto, Brazil
hcfmusp.author.externalESPREAFICO, Enilza Maria:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol, Ribeirao Preto, Brazil
hcfmusp.author.externalPACO-LARSON, Maria Luisa:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol, Ribeirao Preto, Brazil
hcfmusp.author.externalCARLOTTI JR., Carlos Gilberto:NAP USP, Ctr Integrat Syst Biol CISBi, Ribeirao Preto, Brazil; Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, Ribeirao Preto, Brazil
hcfmusp.citation.scopus38
hcfmusp.contributor.author-fmusphcSUELI MIEKO OBA SHINJO
hcfmusp.contributor.author-fmusphcSUELY KAZUE NAGAHASHI MARIE
hcfmusp.description.articlenumbere62200
hcfmusp.description.issue4
hcfmusp.description.volume8
hcfmusp.origemWOS
hcfmusp.origem.pubmed23638004
hcfmusp.origem.scopus2-s2.0-84876727692
hcfmusp.origem.wosWOS:000318341400043
hcfmusp.publisher.citySAN FRANCISCO
hcfmusp.publisher.countryUSA
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
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