CPEB2 m6A methylation regulates blood-tumor barrier permeability by regulating splicing factor SRSF5 stability.
Commun Biol
; 5(1): 908, 2022 09 05.
Article
en En
| MEDLINE
| ID: mdl-36064747
ABSTRACT
The blood-tumor barrier (BTB) contributes to poor therapeutic efficacy by limiting drug uptake; therefore, elevating BTB permeability is essential for glioma treatment. Here, we prepared astrocyte microvascular endothelial cells (ECs) and glioma microvascular ECs (GECs) as in vitro blood-brain barrier (BBB) and BTB models. Upregulation of METTL3 and IGF2BP3 in GECs increased the stability of CPEB2 mRNA through its m6A methylation. CPEB2 bound to and increased SRSF5 mRNA stability, which promoted the ETS1 exon inclusion. P51-ETS1 promoted the expression of ZO-1, occludin, and claudin-5 transcriptionally, thus regulating BTB permeability. Subsequent in vivo knockdown of these molecules in glioblastoma xenograft mice elevated BTB permeability, promoted doxorubicin penetration, and improved glioma-specific chemotherapeutic effects. These results provide a theoretical and experimental basis for epigenetic regulation of the BTB, as well as insight into comprehensive glioma treatment.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Encefálicas
/
Proteínas de Unión al ARN
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Factores de Empalme Serina-Arginina
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Glioma
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Metiltransferasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2022
Tipo del documento:
Article