Epstein-Barr病毒相关胃腺癌p53抑制基因的新发现

Q2 Biochemistry, Genetics and Molecular Biology
Seyed Mohammad Ali Hashemi, Abdolvahab Moradi, Seyed Younes Hosseini, Hadi Razavi Nikoo, Taravat Bamdad, Zahra Faghih, Jamal Sarvari, Alijan Tabarraei
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引用次数: 0

摘要

背景:p53突变在Epstein-Barr病毒相关胃癌中并不常见,但其抑制机制是通过Epstein-Barr病毒核抗原-1 (EBNA1)活性抑制泛素特异性肽酶7 (USP7)。本研究旨在评估EBNA1对p53抑制基因表达的影响以及USP7抑制对p53抑制的影响。方法:用EBNA1质粒转染MKN-45细胞。通过对潮霉素B耐药的筛选,获得了稳定表达EBNA1的细胞株。实时荧光定量PCR检测小鼠双分钟(MDM)4、MDM2、sirtuin (SIRT)3、组蛋白去乙酰化酶(HDAC)1、蛋白酶体26S亚基、非atp酶(PSMD)10、USP7和p53的表达。同时,用GNE-6776处理含有EBNA1或对照质粒的细胞,评估感兴趣基因的表达和细胞存活率。结果:转染EBNA1后,MDM4、MDM2和PSMD10在MKN-45细胞系中显著上调。20天后,观察到携带EBNA1的细胞的形态学变化。在对照细胞中,USP7抑制作用在24 h后显著上调HDAC1、PSMD10、MDM4和MDM2基因,但在4天后下调这些基因。在含有ebna1的细胞中,MDM2、MDM4和PSMD10基因在24 h后显著上调,并且除MDM4外的所有基因在4天后都保持这种作用。此外,USP7抑制诱导两组细胞凋亡。结论:EBNA1增强了p53抑制基因的表达。在USP7蛋白被抑制之后,p53蛋白过表达和凋亡激活两个事件,为其可能的功能提供了证据。EBNA1-USP7相互作用在p53抑制中的意义值得进一步研究并可能重新考虑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A New Insight Into p53-Inhibiting Genes in Epstein–Barr Virus-Associated Gastric Adenocarcinoma

A New Insight Into p53-Inhibiting Genes in Epstein–Barr Virus-Associated Gastric Adenocarcinoma

A New Insight Into p53-Inhibiting Genes in Epstein–Barr Virus-Associated Gastric Adenocarcinoma

A New Insight Into p53-Inhibiting Genes in Epstein–Barr Virus-Associated Gastric Adenocarcinoma

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.

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来源期刊
Iranian Biomedical Journal
Iranian Biomedical Journal Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
3.20
自引率
0.00%
发文量
42
审稿时长
8 weeks
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