PRMT5 promotes retinoblastoma development
Human cell(2022)
摘要
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.
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关键词
Retinoblastoma,Epigenetics,Protein arginine methyltransferase 5,Vascular endothelial growth factor-A,Matrix metalloproteinase
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