Iranian Biomedical Journal

en A New Insight Into p53-Inhibiting Genes in Epstein–Barr Virus-Associated Gastric Adenocarcinoma Cancer Biology Cancer Biology مقاله کامل Full Length/Original Article <div style="text-align: justify;">Background: The p53 mutation is uncommon in Epstein–Barr virus-linked gastric carcinoma, but its suppression occurs through mechanisms such as ubiquitin specific peptidase 7 (USP7) inhibitions via Epstein–Barr virus nuclear antigen-1 (EBNA1) activity. This study aimed to evaluate the effect of EBNA1 on p53-inhibiting gene expression and the impact of USP7 inhibition on p53 suppression. Methods: MKN-45 cells were transfected with the EBNA1 plasmid. A stable EBNA1 expression cell line was developed through selection based on hygromycin B resistance. Murine double minute (MDM)4, MDM2, sirtuin (SIRT)3, histone deacetylase (HDAC)1, proteasome 26S subunit, Non-ATPase (PSMD)10, USP7, and p53 expression were checked using real-time PCR. Also, cells containing EBNA1 or control plasmid were treated with GNE-6776, and the expression of the interested genes and cell survival were assessed. Results: MDM4, MDM2, and PSMD10 were significantly upregulated in the MKN-45 cell line following EBNA1 transfection. Morphological changes were observed in the cells harboring EBNA1 after 20 days. In the control cells, USP7 inhibition significantly upregulated the HDAC1, PSMD10, MDM4, and MDM2 genes after 24 h, but downregulated these genes after four days. In the EBNA1-harboring cells, MDM2, MDM4, and PSMD10 genes were significantly upregulated after 24 h, and this effect was sustained for all genes except for MDM4, even after four days. Furthermore, USP7 inhibition induced apoptosis in both cell groups. Conclusion: EBNA1 enhances the expression of p53-inhibiting genes. Two events—p53 protein overexpression and apoptosis activation—followed the suppression of the USP7 protein and provided evidence for its possible function. The significance of the EBNA1-USP7 interaction in p53 suppression warrants additional investigation and possibly reconsideration.  </div> Herpesvirus 4, Tumor suppressor protein p53, USP7 protein 34 45 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-5038-1&slc_lang=en&sid=1 Seyed Mohammad Ali Hashemi smah.j1992@yahoo.com 0000-0001-8680-6141 No Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Abdolvahab Moradi bmoradi@gmail.com 0000-0003-2877-4190 No Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Seyed Younes Hosseini Hoseini@sums.ac.ir 0000-0002-5881-6796 No Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Hadi Razavi Nikoo hadirazavi96@gmail.com 0000-0001-6028-7208 No Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran Taravat Bamdad bamdat@modares.ac.ir 0000-0003-3620-0701 No Department of Virology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran Zahra Faghih faghl@sums.ac.ir 0000-0002-4563-3069 No Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Jamal Sarvari* sarvarij@sums.ac.ir 0000-0002-2259-0836 No Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Alijan Tabarraei tabarraei@goums.ac.ir 0000-0002-8167-5469 Yes Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran