The Anti-Apoptotic Role of EBV-LMP1 in Lymphoma Cells.

Abstract

BackgroundEpstein-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.MethodsThe 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.ResultsOverexpression 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.ConclusionEBV-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.