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

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Tipo de produção
article
Data de publicação
2024
DOI
Scopus
Web of Science
PubMed
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ISSN da Revista
Título do Volume
Editora
BMC
Autores
BOCCACINO, Jacqueline Marcia
PEIXOTO, Rafael dos Santos
FERNANDES, Camila Felix de Lima
CANGIANO, Giovanni
COELHO, Barbara Paranhos
PRADO, Mariana Brandao
MELO-ESCOBAR, Maria Isabel
SOUSA, Breno Pereira de
AYYADHURY, Shamini
Citação
BMC CANCER, v.24, n.1, article ID 199, 17p, 2024
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
BackgroundGlioblastoma (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.
Palavras-chave
Glioblastoma, Transcriptomics, Prion protein, Intracellular trafficking, Vesicle dynamics
URI
https://observatorio.fm.usp.br/handle/OPI/58921
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE