EBNA۱ Upregulates P۵۳-Inhibiting Genes in Burkitt's Lymphoma Cell Line

  • سال انتشار: 1401
  • محل انتشار: مجله گزارش های بیوشیمی و زیست شناسی مولکولی، دوره: 11، شماره: 4
  • کد COI اختصاصی: JR_RBMB-11-4_014
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 163
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نویسندگان

Seyed Mohammad Ali Hashemi

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

Abdolvahab Moradi

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

Seyed Younes Hosseini

Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Hadi Razavi Nikoo

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

Taravat Bamdad

Department of Virology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.

Mahboobeh Razmkhah

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

Jamal Sarvari

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*

Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

چکیده

Background: Suppression of p۵۳ is an important mechanism in Epstein-Barr virus associate-tumors and described as EBNA۱-USP۷ which is a key axis in p۵۳ suppression. Thus, in this study, we aimed to evaluate the function of EBNA۱ on the expression of p۵۳-inhibiting genes including HDAC-۱, MDM۲, MDM۴, Sirt-۳, and PSMD۱۰ and the influence of USP۷ inhibition using GNE-۶۷۷۶ on p۵۳ at protein/mRNA level. Methods:  The electroporation method was used to transfect the BL۲۸ cell line with EBNA۱. Cells with stable EBNA۱ expression were selected by Hygromycin B treatment. The expression of seven genes, including PSMD۱۰, HDAC-۱, USP۷, MDM۲, P۵۳, Sirt-۳, and MDM۴, was evaluated using a real-time PCR assay. For evaluating the effects of USP۷ inhibition, the cells were treated with GNE-۶۷۷۶; after ۲۴ hours and ۴ days, the cells were collected and again expression of interest genes was evaluated. Results: MDM۲ (P=۰.۰۲۸), MDM۴ (P=۰.۰۲۸), USP۷ (P=۰.۰۲۸), and HDAC۱ (P=۰.۰۱۵) all showed significantly higher expression in EBNA۱-harboring cells compared to control plasmid transfected cells, while p۵۳ mRNA expression was only marginally downregulated in EBNA۱ harboring cells (P=۰.۶۸۵). Four-day after treatment, none of the studied genes was significantly changed. Also, in the first ۲۴-hour after treatment, mRNA expression of p۵۳ was downregulated (P=۰.۶۸۵), but after ۴ days it was upregulated (P=۰.۷) insignificantly. Conclusions: It seems that EBNA۱ could strongly upregulate p۵۳-inhibiting genes including HDAC۱, MDM۲, MDM۴, and USP۷. Moreover, it appears that the effects of USP۷ suppression on p۵۳ at protein/mRNA level depend on the cell nature; however, further research is needed.

کلیدواژه ها

Keywords: Epstein-Barr virus, EBNA۱, P۵۳, USP۷, P۵۳-inhibiting Genes.

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