Cancer Management and Research (Sep 2020)
The Anti-Apoptotic Role of EBV-LMP1 in Lymphoma Cells
Abstract
Mei Zeng,1,* Yuhua Chen,2,* Xintao Jia,2 Yan Liu2 1Pathology Teaching and Research Section, Xiangyang Polytechnic, Xiangyang 441021, Hubei, People’s Republic of China; 2Department of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xintao Jia; Yan LiuDepartment of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangcheng County, Xiangyang 441021, Hubei, People’s Republic of ChinaTel/Fax +86-0710-3524082Email [email protected]; [email protected]: Epstein-Barr virus (EBV) has been indicated in the development of some tumors, including lymphoma. However, the potential role of latent membrane protein 1 (LMP1) encoded by EBV in the tumorigenesis of lymphoma remains debated. Herein, we examined the function of LMP1 in lymphoma.Methods: The expression of LMP1 was downregulated or upregulated in EBV negative cell line SNT-8 and positive cell line KHYG-1, respectively. Subsequently, the cell viability, apoptosis, as well as the expression patterns of p53, mouse double minute 2 (MDM2), B-cell CLL/lymphoma 2 (Bcl-2) and NF-κB were evaluated. Next, the binding relationship between MDM2 and p53 along with p53 ubiquitination in cells was tested by Western blot and co-immunoprecipitation. Finally, the effects of LMP1 on lymphoma cell growth through p53, Bcl-2 and NF-κB pathways were verified by functional rescue experiments.Results: Overexpression of LMP1 promoted KHYG-1 cell growth and inhibited cell apoptosis. Moreover, LMP1 upregulation significantly enhanced the activation of NF-κB pathway, thus increasing MDM2 binding to p53, leading to p53 ubiquitination and degradation as well as Bcl-2 expression enhancement. Further inhibition of the NF-κB pathway or Bcl-2 expression significantly weakened the promotive role of LMP1 in the growth of KHYG-1 cells.Conclusion: EBV-LMP1 promoted the p53 ubiquitination and degradation by activating NF-κB signaling pathway and the following binding of MDM2 and p53 in cells to enhance Bcl-2 expression, thus promoting the growth of lymphoma cells and inhibiting cell apoptosis.Keywords: EBV-LMP1, p53, MDM2, ubiquitination and degradation, lymphadenoma, apoptosis
