LMP2A suppresses the role of AHR pathway through ERK signal pathway in EBV-associated gastric cancer

Abstract

Objective: To investigate the function of the aryl hydrocarbon receptor (AHR) pathway in Epstein-Barr Virus (EBV)-associated gastric cancer (EBVaGC) and to explore the relationship between EBV and AHR expression. Methods: The expression of AHR in EBVaGC and EBV negative GC (EBVnGC) tissues was detected by immunohistochemistry (IHC). Real-time qPCR (RT-qPCR) and Western blot analysis were used to examine the expression of AHR, cytochrome P450 1A1 (CYP1A1), and cytochrome P450 1B1 (CYP1B1) in gastric cancer cells. The cell proliferation and migration assay were tested by CCK8 and transwell analysis. EBV-encoded latent membrane protein 2A (LMP2A) was over-expressed in SGC7901 cells and silenced in AGS-EBV cells to further identify its role in EBV positive GC cells. Results: It was found that EBV infection inhibited the expression of AHR in gastric cancer tissues and cell lines. We also found that the activation of AHR pathway can promote cell proliferation and migration. However, the function was restricted in EBVaGC cell lines compared with EBVnGC. LMP2A can suppress AHR expression and pathway activation by activating phosphorylation of extracellular signal-regulated kinase (ERK) in EBV positive GC cell lines. Conclusion: EBV-encoded LMP2A regulated the function of the AHR pathway by activating the ERK signal pathway in EBV positive GC cell lines.