EBV-LMP1 regulating AKT/mTOR signaling pathway and WWOX in nasopharyngeal carcinoma

Our previous studies found the expression of tumor suppressor gene WWOX was reduced in nasopharyngeal carcinoma (NPC), and WWOX expression gradually declined with the progress and lymph node metastasis in patients. These suggested that WWOX was related with the development of NPC. AKT/mTOR signaling pathway was considered the primary pathway of cancer cell survival. AKT/mTOR pathway and WWOX had been found to be closely related. NPC was closely related to infection of Epstein-Barr virus (EBV). The study mainly used oncogene LMP1 of EBV as a starting point to explore whether LMP1 regulated the AKT/mTOR signaling pathway and WWOX gene. Western blot and qPCR were used to detect the expression of AKT/mTOR pathway (AKT, p-AKT, p70S6K and p-p70S6K) and WWOX in nasopharyngeal carcinoma cell lines CNE1 and CNE1-LMP1, and accessed relationship of LMP1 with AKT/mTOR and WWOX. Research of correlation between LMP1 and WWOX gene expression suggested that in CNE1-LMP1 cells, WWOX gene and protein levels were decreased compared with CNE1 cells (P=0.025, P=0.042, respectively). The difference was statistically significant, and suggested that LMP1 expression correlated with WWOX. Research of correlation between LMP1 and AKT/mTOR signaling pathway demonstrated that when cell line CNE1-LMP1 was compared with CNE1 in AKT/mTOR pathway key protein of AKT, p-AKT, p70S6K and p-p70S6K expression, P values were 0.075, 0.008, 0.124, 0.034, respectively, and expression of p-AKT, p-p70S6K in CNE1-LMP1 were higher than CNE1, which were significantly different from each other. It suggested AKT/mTOR pathway was regulated by LMP1. WWOX gene and AKT/mTOR signaling pathway were regulated by the EBV-LMP1 oncogene.