PRMT5 promotes retinoblastoma development.
Hum Cell
; 36(1): 329-341, 2023 Jan.
Article
em En
| MEDLINE
| ID: mdl-36331723
ABSTRACT
Epigenetic mechanism, including DNA methylation and histone modifications, contributes to alterations in the expression patterns of genes regulating malignant phenotype of cancer cells. However, the epigenetic modulation of vascular endothelial growth factor-A (VEGFA) in retinoblastoma (RB) has not been clearly established. We aimed to examine the epigenetic regulation of VEGFA by protein arginine methyltransferase 5 (PRMT5) in RB. Using the GEO database, we identified VEGFA as a pathogenic gene in RB. Silencing of VEGFA in SO-RB50 and Y79 cells inhibited cell proliferation, angiogenesis, and migration, promoted apoptosis, and suppressed tumor growth in mice. Mechanistically, PRMT5 promoted H3K4me3 modification of the VEGFA promoter, thereby activating VEGFA expression. VEGFA could regulate the expression of MMP1, MMP2, and MMP9. Further silencing of VEGFA in RB cells overexpressing PRMT5 constrained the expression of MMP1, MMP2 and MMP9, and suppressed the growth of tumors in mice. In conclusion, this study clarifies that the depletion of PRMT5 reduces H3K4me3-mediated VEGFA transcription and retards the carcinogenesis of RB by suppressing the expression of MMPs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retinoblastoma
/
Neoplasias da Retina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Hum Cell
Ano de publicação:
2023
Tipo de documento:
Article