ID2-ETS2 axis regulates the transcriptional acquisition of pro-tumoral microglia phenotype in glioma.
Inhibitor of Differentiation Protein 2
/ metabolism
Microglia
/ metabolism
Proto-Oncogene Protein c-ets-2
/ metabolism
Humans
Glioma
/ genetics
Animals
Proto-Oncogene Mas
Cell Line, Tumor
Phenotype
Gene Expression Regulation, Neoplastic
Brain Neoplasms
/ genetics
Transcription, Genetic
Rats
Glioblastoma
/ genetics
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
18 Jul 2024
18 Jul 2024
Historique:
received:
18
02
2024
accepted:
09
07
2024
revised:
04
07
2024
medline:
18
7
2024
pubmed:
18
7
2024
entrez:
17
7
2024
Statut:
epublish
Résumé
Glioblastoma is a highly aggressive brain tumour that creates an immunosuppressive microenvironment. Microglia, the brain's resident immune cells, play a crucial role in this environment. Glioblastoma cells can reprogramme microglia to create a supportive niche that promotes tumour growth. However, the mechanisms controlling the acquisition of a transcriptome associated with a tumour-supportive microglial reactive state are not fully understood. In this study, we investigated changes in the transcriptional profile of BV2 microglia exposed to C6 glioma cells. RNA-sequencing analysis revealed a significant upregulation of microglial inhibitor of DNA binding 1 (Id1) and Id2, helix-loop-helix negative transcription regulatory factors. The concomitant regulation of microglial ETS proto-oncogene 2, transcription factor (ETS2)-target genes, i.e., Dusp6, Fli1, Jun, Hmox1, and Stab1, led us to hypothesize that ETS2 could be regulated by ID proteins. In fact, ID2-ETS2 protein interactions increased in microglia exposed to glioma cells. In addition, perturbation of the ID2-ETS2 transcriptional axis influenced the acquisition of a microglial tumour-supportive phenotype. ID2 and ETS2 genes were found to be expressed by the tumour-associated microglia isolated from human glioblastoma tumour biopsies. Furthermore, ID2 and ETS2 gene expressions exhibited inverse prognostic values in patients with glioma in cohorts from The Cancer Genome Atlas. Collectively, our findings indicate that the regulation of ETS2 by ID2 plays a role in the transcriptional regulation of microglia in response to stimuli originating from glioblastoma cells, information that could lead to developing therapeutic strategies to manipulate microglial tumour-trophic functions.
Identifiants
pubmed: 39019900
doi: 10.1038/s41419-024-06903-3
pii: 10.1038/s41419-024-06903-3
doi:
Substances chimiques
Inhibitor of Differentiation Protein 2
0
Proto-Oncogene Protein c-ets-2
0
Proto-Oncogene Mas
0
MAS1 protein, human
0
ID2 protein, human
0
ETS2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
512Informations de copyright
© 2024. The Author(s).
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