Expression of MAP9 in Epstein-Barr virus-associated gastric carcinoma.

Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) comprises approximately 9% of all cases of GC. EBV-associated GC (EBVaGC) has characteristic clinicopathological features for a favorable prognosis. Microtubule-associated protein 9 (MAP9) is a cell cycle-associated gene required for bipolar spindle assembly, mitosis progression, and cytokinesis. Nevertheless, to date, there have been no reports on MAP9 function in EBVaGC. In this study, we demonstrated that the mRNA and protein levels of MAP9 were up-regulated in EBV-positive gastric carcinoma cell lines. The positive rate of MAP9 expression in EBVaGC tissues was shown to be significantly higher than that in EBV-negative gastric carcinoma (EBVnGC) tissues. Additionally, the expression of MAP9 was partly increased in EBVnGC cell lines by interfering with DNA methyltransferase 1 (DNMT1) or treated with 5-aza-2'-deoxycytidine. Thus, EBV may regulate MAP9 expression by modifying the methylation of MAP9 CpG islands through DNMT1. By inhibiting the expression of MAP9 with small interfere sequence in the EBV-positive GC cell line GT38 and overexpressing MAP9 in the EBV-negative GC cell line AGS, we demonstrated that MAP9 inhibited the growth and induced apoptosis of EBVaGC cells significantly. In conclusion, our study demonstrated that EBV can up-regulate the expression of MAP9 in EBVaGC, and the methylation of MAP9 CpG islands influences this regulation. And MAP9 acts as a tumor suppressor in the development of EBVaGC.