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

Autor: Boccacino JM; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., Dos Santos Peixoto R; Department of Automation and Systems, Technological Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Fernandes CFL; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., Cangiano G; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., Sola PR; Cellular and Molecular Biology Laboratory (LIM 15), Department of Neurology, Faculdade de Medicina (FMUSP), University of Sao Paulo, Sao Paulo, Brazil., Coelho BP; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., Prado MB; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., Melo-Escobar MI; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., de Sousa BP; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil., Ayyadhury S; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada., Bader GD; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Department of Computer Science, University of Toronto, Toronto, Ontario, Canada., Shinjo SMO; Cellular and Molecular Biology Laboratory (LIM 15), Department of Neurology, Faculdade de Medicina (FMUSP), University of Sao Paulo, Sao Paulo, Brazil., Marie SKN; Cellular and Molecular Biology Laboratory (LIM 15), Department of Neurology, Faculdade de Medicina (FMUSP), University of Sao Paulo, Sao Paulo, Brazil., da Rocha EL; Department of Microbiology, Immunology, and Parasitology, Biological Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil. edroaldo.lummertz@ufsc.br., Lopes MH; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 room 431, Sao Paulo, 05508000, Brazil. marilenehl@usp.br.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2024 Feb 13; Vol. 24 (1), pp. 199. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1186/s12885-024-11914-6
Abstrakt: Background: Glioblastoma (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 (PrP C ) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrP C can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness. Nevertheless, the exact molecular mechanisms through which PRNP/PrP C modulates key aspects of GBM biology remain elusive.
Methods: To elucidate the implications of PRNP/PrP C 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 PRNP high and PRNP low 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/PrP C might function in this tumor. We explored an additional proteomics dataset, applying similar comparative approaches, to corroborate our findings.
Results: Functional profiling revealed that vesicular dynamics signatures are strongly correlated with PRNP/PrP C levels in GBM. We found a panel of 73 genes, enriched in vesicle-related pathways, whose expression levels are increased in PRNP high /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 PRNP high /PRNP + GBM cells.
Conclusions: Together, our findings shed light on a novel role for PrP C 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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