Zeng M, Chen Y, Jia X, Liu Y

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.The expression of LMP1 was downregulated or upregulated ...

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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-?B 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-?B pathways were verified by functional rescue experiments.Overexpression of LMP1 promoted KHYG-1 cell growth and inhibited cell apoptosis. Moreover, LMP1 upregulation significantly enhanced the activation of NF-?B 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-?B pathway or Bcl-2 expression significantly weakened the promotive role of LMP1 in the growth of KHYG-1 cells.EBV-LMP1 promoted the p53 ubiquitination and degradation by activating NF-?B 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.

Date: Oct. 17, 2020

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