Unraveling the Aurora kinase A and Epstein-Barr nuclear antigen 1 axis in Epstein Barr virus associated gastric cancer.

ABSTRACT

Aurora kinase A (AURKA) is one of the crucial cell cycle regulators associated with gastric cancer. Here, we explored Epstein Barr Virus-induced gastric cancer progression through EBV protein EBNA1 with AURKA. We found that EBV infection enhanced cell proliferation and migration of AGS cells and upregulation of AURKA levels. AURKA knockdown markedly reduced the proliferation and migration of the AGS cells even with EBV infection. Moreover, MD-simulation data deciphered the probable connection between EBNA1 and AURKA. The in-vitro analysis through the transcript and protein expression showed that AURKA knockdown reduces the expression of EBNA1. Moreover, EBNA1 alone can enhance AURKA protein expression in AGS cells. Co-immunoprecipitation and NMR analysis between AURKA and EBNA1 depicts the interaction between two proteins. In addition, AURKA knockdown promotes apoptosis in EBV-infected AGS cells through cleavage of Caspase-3, -9, and PARP1. This study demonstrates that EBV oncogenic modulators EBNA1 possibly modulate AURKA in EBV-mediated gastric cancer progression.