Epstein-Barr virus nuclear antigen 1 upregulates Derlin1 and PSMD10 expression in HeLa cells
Amir Hossein Alipour1,2,*, Seyed Mohammad Ali Hashemi1,*, Fatemeh Gharahkhani1, Alireza Katanchi1, Ali Farhadi1, and Jamal Sarvari1,4
1 Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
3 Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
4 Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
* These authors contributed equally to this work
Correspondence to:
Jamal Sarvari, email: [email protected]
Keywords: cervical carcinoma; Epstein–Barr virus; EBNA1
Received: November 10, 2024 Accepted: July 24, 2025 Published: August 06, 2025
Abstract
Background: Epstein-Barr Virus (EBV), a potent viral carcinogen, plays a crucial role in the development of various malignancies. Among its proteins, EBV nuclear antigen-1 (EBNA1) stands out for its ability to modulate gene expression. In this study, we explored the impact of EBNA1 on the expression patterns of four cellular genes—Derlin1, ZEB1, CNN3, and PSMD10—in HeLa cells.
Materials and Methods: Three distinct categories of HeLa cells were established:
1. EBNA1-Transfected Cells: These cells were transfected with the EBNA1 gene.
2. Control Plasmid-Transfected Cells: These cells received transfection with a control plasmid.
3. Non-Transfected Cells (Control Group): These cells were not subjected to any transfection.
After RNA extraction, we employed real-time PCR to evaluate the transcriptional levels of four specific genes—Derlin 1, ZEB1, CNN3, and PSMD10—in each of the three cell groups. The Mann-Whitney U-test was subsequently utilized to compare means, and statistical significance was determined based on p-values below 0.05. Data were meticulously recorded in an Excel 2016 spreadsheet.
Results: The results demonstrated that HeLa cells transfected with the EBNA1 plasmid exhibited significantly increased expression levels of Derlin1 (p = 0.028) and PSMD10 (p = 0.028) genes compared to cells transfected with the control plasmid. However, the expression changes observed in CNN3 and ZEB1 were not statistically significant (p = 0.99 and p = 0.2, respectively).
Conclusions: Our findings suggest that increase expression levels of Derlin1 and PSMD10 genes in HeLa cells by the EBV-EBNA1 might induce cancer cell survival and accelerates the development of cervical cancer (CC). However, to establish a conclusive link between EBV-EBNA1 and CC progression, further investigations are warranted.
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