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PRMT5 promotes retinoblastoma development.

Yu Jiang1,2, Guangying Zheng3, Xiantao Sun2

  • 1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe Road, Zhengzhou, 450000, Henan, People's Republic of China.

Human Cell
|November 4, 2022
PubMed
Summary
This summary is machine-generated.

Protein arginine methyltransferase 5 (PRMT5) epigenetically activates vascular endothelial growth factor-A (VEGFA) in retinoblastoma. PRMT5 depletion inhibits VEGFA, suppressing cancer growth and matrix metalloproteinase expression.

Keywords:
EpigeneticsMatrix metalloproteinaseProtein arginine methyltransferase 5RetinoblastomaVascular endothelial growth factor-A

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Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Epigenetic alterations drive cancer progression by modifying gene expression.
  • The role of epigenetic regulation of vascular endothelial growth factor-A (VEGFA) in retinoblastoma (RB) remains unclear.

Purpose of the Study:

  • To investigate the epigenetic regulation of VEGFA by protein arginine methyltransferase 5 (PRMT5) in RB.
  • To elucidate the mechanism by which PRMT5 influences VEGFA expression and RB carcinogenesis.

Main Methods:

  • Utilized the GEO database to identify VEGFA as a pathogenic gene in RB.
  • Performed gene silencing experiments in RB cell lines (SO-RB50, Y79) and in vivo tumor models.
  • Analyzed histone modifications (H3K4me3) at the VEGFA promoter and expression of matrix metalloproteinases (MMPs).

Main Results:

  • VEGFA silencing inhibited RB cell proliferation, angiogenesis, migration, and tumor growth, while promoting apoptosis.
  • PRMT5 was found to activate VEGFA transcription via H3K4me3 modification of the VEGFA promoter.
  • VEGFA regulated MMP1, MMP2, and MMP9 expression; PRMT5 depletion reduced MMP expression and tumor growth.

Conclusions:

  • PRMT5 epigenetically upregulates VEGFA expression in RB through H3K4me3 modification.
  • Targeting PRMT5 reduces VEGFA and MMP expression, thereby inhibiting retinoblastoma progression and tumor growth.