Abstract

Aquaporin 3(AQP3) is involved in epithelial-mesenchymal transformation of tumor cells and is closely related to the occurrence and development of tumors. However, the regulatory mechanism and function of AQP3 in EBV-associated gastric cancer (EBVaGC) are still poorly understood. This study aims to explore the regulatory effect of EBV on AQP3 and the cross talk of AQP3 with EIF4E-binding proteins 1(4E-BP1) in EBVaGC. The effect of LMP2A on the expression of AQP3 and 4E-BP1 was analyzed using real-time PCR and western blotting. The biological functions of AQP3 and 4E-BP1 in gastric cancer cells were detected by cell biological experiments. In addition, we examined the role of mTOR and ERK signaling pathways in the LMP2A/AQP3/4E-BP1 regulatory axis. We found that LMP2A could down-regulate AQP3 expression by inhibiting the activation of mTOR signaling pathway, and further promote autophagy and migration of gastric cancer cells. AQP3 up-regulated the expression of 4E-BP1 and its phosphorylated protein by activating ERK signaling pathway, thus promoting the autophagy and proliferation of gastric cancer cells. In conclusion, EBV-encoded LMP2A inhibits AQP3 expression, and further participates in cell proliferation, migration and autophagy through the mTOR/AQP3/ERK/4E-BP1 axis.

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