Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas

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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.authorBOCCACINO, Jacqueline Marcia
dc.contributor.authorPEIXOTO, Rafael dos Santos
dc.contributor.authorFERNANDES, Camila Felix de Lima
dc.contributor.authorCANGIANO, Giovanni
dc.contributor.authorSOLA, Paula Rodrigues
dc.contributor.authorCOELHO, Barbara Paranhos
dc.contributor.authorPRADO, Mariana Brandao
dc.contributor.authorMELO-ESCOBAR, Maria Isabel
dc.contributor.authorSOUSA, Breno Pereira de
dc.contributor.authorAYYADHURY, Shamini
dc.contributor.authorBADER, Gary D.
dc.contributor.authorSHINJO, Sueli Mieko Oba
dc.contributor.authorMARIE, Suely Kazue Nagahashi
dc.contributor.authorROCHA, Edroaldo Lummertz da
dc.contributor.authorLOPES, Marilene Hohmuth
dc.date.accessioned2024-04-05T19:32:41Z
dc.date.available2024-04-05T19:32:41Z
dc.date.issued2024
dc.description.abstractBackgroundGlioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrPC) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrPC can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness. Nevertheless, the exact molecular mechanisms through which PRNP/PrPC modulates key aspects of GBM biology remain elusive.MethodsTo elucidate the implications of PRNP/PrPC in the biology of this cancer, we analyzed publicly available RNA sequencing (RNA-seq) data of patient-derived GBMs from four independent studies. First, we ranked samples profiled by bulk RNA-seq as PRNPhigh and PRNPlow and compared their transcriptomic landscape. Then, we analyzed PRNP+ and PRNP- GBM cells profiled by single-cell RNA-seq to further understand the molecular context within which PRNP/PrPC might function in this tumor. We explored an additional proteomics dataset, applying similar comparative approaches, to corroborate our findings.ResultsFunctional profiling revealed that vesicular dynamics signatures are strongly correlated with PRNP/PrPC levels in GBM. We found a panel of 73 genes, enriched in vesicle-related pathways, whose expression levels are increased in PRNPhigh/PRNP+ cells across all RNA-seq datasets. Vesicle-associated genes, ANXA1, RAB31, DSTN and SYPL1, were found to be upregulated in vitro in an in-house collection of patient-derived GBM. Moreover, proteome analysis of patient-derived samples reinforces the findings of enhanced vesicle biogenesis, processing and trafficking in PRNPhigh/PRNP+ GBM cells.ConclusionsTogether, our findings shed light on a novel role for PrPC as a potential modulator of vesicle biology in GBM, which is pivotal for intercellular communication and cancer maintenance. We also introduce GBMdiscovery, a novel user-friendly tool that allows the investigation of specific genes in GBM biology.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.indexWoS
dc.description.sponsorshipFundao de Amparo Pesquisa do Estado de So Paulo
dc.identifier.citationBMC CANCER, v.24, n.1, article ID 199, 17p, 2024
dc.identifier.doi10.1186/s12885-024-11914-6
dc.identifier.eissn1471-2407
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/58921
dc.language.isoeng
dc.publisherBMCeng
dc.relation.ispartofBMC Cancer
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright BMCeng
dc.subjectGlioblastomaeng
dc.subjectTranscriptomicseng
dc.subjectPrion proteineng
dc.subjectIntracellular traffickingeng
dc.subjectVesicle dynamicseng
dc.subject.otherstress-inducible protein-1eng
dc.subject.othercellular prioneng
dc.subject.otherextracellular vesicleseng
dc.subject.otherclassificationeng
dc.subject.otherproliferationeng
dc.subject.othertransporteng
dc.subject.othertargetseng
dc.subject.othersurfaceeng
dc.subject.othergrowtheng
dc.subject.otherrnaeng
dc.subject.wosOncologyeng
dc.titleIntegrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomaseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryisoca
hcfmusp.author.externalBOCCACINO, Jacqueline Marcia:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalPEIXOTO, Rafael dos Santos:Univ Fed Santa Catarina, Technol Ctr, Dept Automat & Syst, Florianopolis, SC, Brazil
hcfmusp.author.externalFERNANDES, Camila Felix de Lima:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalCANGIANO, Giovanni:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalCOELHO, Barbara Paranhos:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalPRADO, Mariana Brandao:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalMELO-ESCOBAR, Maria Isabel:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalSOUSA, Breno Pereira de:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.author.externalAYYADHURY, Shamini:Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada; Univ Toronto, Donnelly Ctr, Toronto, ON, Canada
hcfmusp.author.externalBADER, Gary D.:Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada; Univ Toronto, Donnelly Ctr, Toronto, ON, Canada; Univ Toronto, Dept Mol Genet, Toronto, ON, Canada; Univ Toronto, Dept Comp Sci, Toronto, ON, Canada
hcfmusp.author.externalROCHA, Edroaldo Lummertz da:Univ Fed Santa Catarina, Biol Sci Ctr, Dept Microbiol Immunol & Parasitol, BR-88040900 Florianopolis, SC, Brazil
hcfmusp.author.externalLOPES, Marilene Hohmuth:Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Av Prof Lineu Prestes,1524 Room 431, BR-05508000 Sao Paulo, Brazil
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcPAULA RODRIGUES SOLA
hcfmusp.contributor.author-fmusphcSUELI MIEKO OBA SHINJO
hcfmusp.contributor.author-fmusphcSUELY KAZUE NAGAHASHI MARIE
hcfmusp.description.articlenumber199
hcfmusp.description.issue1
hcfmusp.description.volume24
hcfmusp.origemWOS
hcfmusp.origem.dimensionspub.1168795479
hcfmusp.origem.pubmed38347462
hcfmusp.origem.scopus2-s2.0-85185142756
hcfmusp.origem.wosWOS:001160557500001
hcfmusp.publisher.cityLONDONeng
hcfmusp.publisher.countryENGLANDeng
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