Centromere protein J is overexpressed in human glioblastoma and promotes cell proliferation and migration.

Autor: de Freitas GPA; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Geraldo LHM; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Yale Cardiovascular Research Center, Yale University, New Haven, Connecticut, USA., Faria BM; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Department of Cell Biology, Yale University, New Haven, Connecticut, USA., Alves-Leon SV; Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil., de Souza JM; Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil., Moura-Neto V; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Instituto do cérebro Paulo Niemeyer, RJ, Brazil., Pontes B; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Romão LF; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Garcez PP; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2022 Sep; Vol. 162 (6), pp. 501-513. Date of Electronic Publication: 2022 Jul 25.
DOI: 10.1111/jnc.15660
Abstrakt: Glioblastoma is the most common and malignant type of primary brain tumor. Previous studies have shown that alterations in centrosome amplification and its components are frequently found in treatment-resistant tumors and may be associated with tumor progression. A centrosome protein essential for centrosome biogenesis is the centromere protein J (CENPJ), known to control the proliferation of neural progenitors and hepatocarcinoma cells, and also neuronal migration. However, it remains unknown the role of CENPJ in glioblastoma. Here we show that CENPJ is overexpressed in human glioblastoma cell lines in comparison to human astrocytes. Using bioinformatics analysis, we find that high Cenpj expression is associated with poor prognosis in glioma patients. Examining Cenpj loss of function in glioblastoma by siRNA transfection, we find impairments in cell proliferation and migration. Using a Cenpj mutant version with the deleted PN2-3 or TCP domain, we found that a conserved PN2-3 region is required for glioblastoma migration. Moreover, Cenpj downregulation modulates glioblastoma morphology resulting in microtubules stabilization and actin filaments depolymerization. Altogether, our findings indicate that CENPJ controls relevant aspects of glioblastoma progression and might be a target for therapeutic intervention and a biomarker for glioma malignancy.
(© 2022 International Society for Neurochemistry.)
Databáze: MEDLINE
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