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EBNA1 Upregulates P53-Inhibiting Genes in Burkitt's Lymphoma Cell Line

Seyed Mohammad Ali Hashemi1, Abdolvahab Moradi1, Seyed Younes Hosseini2

  • 1Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

Reports of Biochemistry & Molecular Biology
|May 3, 2023
PubMed
Abstract

Insights

Epstein-Barr virus nuclear antigen 1 (EBNA1) upregulates p53-inhibiting genes like HDAC1, MDM2, MDM4, and USP7. USP7 inhibition effects on p53 depend on cell type, requiring further investigation.

Area of Science:

  • Molecular Biology
  • Virology
  • Cancer Research

Background:

  • p53 suppression is crucial in Epstein-Barr virus (EBV)-associated tumors.
  • The EBNA1-USP7 axis is a key player in p53 suppression.
  • Understanding EBNA1's role in regulating p53-inhibiting genes is vital.

Purpose of the Study:

  • To evaluate EBNA1's function on p53-inhibiting genes (HDAC1, MDM2, MDM4, Sirt-3, PSMD10).
  • To assess the influence of USP7 inhibition using GNE-6776 on p53 expression.
  • To investigate the EBNA1-USP7 interaction in the context of EBV-associated malignancies.

Main Methods:

  • BL28 cell line transfection with EBNA1 via electroporation.
  • Stable EBNA1 expression selection using Hygromycin B.
  • Real-time PCR to evaluate gene expression (PSMD10, HDAC-1, USP7, MDM2, P53, Sirt-3, MDM4) pre- and post-GNE-6776 treatment.

Main Results:

  • EBNA1 significantly upregulated MDM2, MDM4, USP7, and HDAC1 mRNA expression (P<0.05).
  • p53 mRNA expression showed only marginal downregulation in EBNA1-harboring cells (P=0.685).
  • USP7 inhibition with GNE-6776 did not significantly alter studied gene expression after 24 hours or 4 days.

Conclusions:

  • EBNA1 strongly upregulates key p53-inhibiting genes: HDAC1, MDM2, MDM4, and USP7.
  • The impact of USP7 suppression on p53 levels is cell-type dependent.
  • Further research is necessary to elucidate the precise mechanisms and therapeutic potential.
Keywords:
EBNA1Epstein-Barr virusP53P53-inhibiting GenesUSP7

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