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en EBNA1 Upregulates P53-Inhibiting Genes in Burkitt's Lymphoma Cell Line میکروب شناسی Microbiology مقالات اصلی Original Article <div style="text-align: justify;">Background: Suppression of p53 is an important mechanism in Epstein-Barr virus associate-tumors and described as EBNA1-USP7 which is a key axis in p53 suppression. Thus, in this study, we aimed to evaluate the function of EBNA1 on the expression of p53-inhibiting genes including HDAC-1, MDM2, MDM4, Sirt-3, and PSMD10 and the influence of USP7 inhibition using GNE-6776 on p53 at protein/mRNA level. Methods:  The electroporation method was used to transfect the BL28 cell line with EBNA1. Cells with stable EBNA1 expression were selected by Hygromycin B treatment. The expression of seven genes, including PSMD10, HDAC-1, USP7, MDM2, P53, Sirt-3, and MDM4, was evaluated using a real-time PCR assay. For evaluating the effects of USP7 inhibition, the cells were treated with GNE-6776; after 24 hours and 4 days, the cells were collected and again expression of interest genes was evaluated. Results: MDM2 (P=0.028), MDM4 (P=0.028), USP7 (P=0.028), and HDAC1 (P=0.015) all showed significantly higher expression in EBNA1-harboring cells compared to control plasmid transfected cells, while p53 mRNA expression was only marginally downregulated in EBNA1 harboring cells (P=0.685). Four-day after treatment, none of the studied genes was significantly changed. Also, in the first 24-hour after treatment, mRNA expression of p53 was downregulated (P=0.685), but after 4 days it was upregulated (P=0.7) insignificantly. Conclusions: It seems that EBNA1 could strongly upregulate p53-inhibiting genes including HDAC1, MDM2, MDM4, and USP7. Moreover, it appears that the effects of USP7 suppression on p53 at protein/mRNA level depend on the cell nature; however, further research is needed.</div> Keywords: Epstein-Barr virus, EBNA1, P53, USP7, P53-inhibiting Genes. 672 683 http://rbmb.net/browse.php?a_code=A-10-1095-1&slc_lang=en&sid=1 Seyed Mohammad Ali Hashemi 100319475328460016845 100319475328460016845 No Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Abdolvahab Moradi 100319475328460016846 100319475328460016846 No Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Seyed Younes Hosseini 100319475328460016847 100319475328460016847 No Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Hadi Razavi Nikoo 100319475328460016848 100319475328460016848 No Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Taravat Bamdad 100319475328460016849 100319475328460016849 No Department of Virology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran. Mahboobeh Razmkhah 100319475328460016850 100319475328460016850 No Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran & Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. Jamal Sarvari sarvarij@sums.ac.ir 100319475328460016851 100319475328460016851 Yes Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran & Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Alijan Tabarraei* tabarraei@goums.ac.ir 100319475328460016852 100319475328460016852 No Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.