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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Glioblastoma | Research

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

Authors: Jacqueline Marcia Boccacino, Rafael dos Santos Peixoto, Camila Felix de Lima Fernandes, Giovanni Cangiano, Paula Rodrigues Sola, Bárbara Paranhos Coelho, Mariana Brandão Prado, Maria Isabel Melo-Escobar, Breno Pereira de Sousa, Shamini Ayyadhury, Gary D. Bader, Sueli Mieko Oba Shinjo, Suely Kazue Nagahashi Marie, Edroaldo Lummertz da Rocha, Marilene Hohmuth Lopes

Published in: BMC Cancer | Issue 1/2024

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Abstract

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 (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.

Methods

To 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.

Results

Functional 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.

Conclusions

Together, 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.
Appendix
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Metadata
Title
Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Authors
Jacqueline Marcia Boccacino
Rafael dos Santos Peixoto
Camila Felix de Lima Fernandes
Giovanni Cangiano
Paula Rodrigues Sola
Bárbara Paranhos Coelho
Mariana Brandão Prado
Maria Isabel Melo-Escobar
Breno Pereira de Sousa
Shamini Ayyadhury
Gary D. Bader
Sueli Mieko Oba Shinjo
Suely Kazue Nagahashi Marie
Edroaldo Lummertz da Rocha
Marilene Hohmuth Lopes
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11914-6

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