| Background & Aims: Documented reports on the axon guidance protein Semaphorin 3E(Sema3E) have revealed that Sema3 E promotes tumor metastasis or/and suppresses tumor cell death. However, the role of Sema3 E in the pathogenesis of gastric cancer and the mechanism that leads to the aberrant expression of Sema3 E in cancer are still unclear. The aim of the present study was to identify the role of Sema3 E in the genesis and progression of gastric cancer as well as the epigenetic mechanism involved in aberrant expression of Sema3 E in gastric cancer.Methods: PCR and tissue array were used to analyze the expression of Sema3 E in gastric cancer in the level of mRNA and protein respectively; Usage of specific small molecular inhibitor DAC, TSA, MGCD0103, MC1568, C646, overexpression and knock-down of p300, and luciferase report assay were used to look into epigenetic regulation mechanism in SEMA3 E transcription in gastric cancer; Vector for eukaryotic expression of SEMA3 E was constructed. The alternation of cell proliferation, colony formation, xenograft tumourigenicity, in vitro migration and invasion of gastric cancer cell lines were examined after Sema3 E overexpression.Results: Here, we demonstrated that Sema3 E is frequently decreased in gastric cancer and that its expression level is inversely associated with tumor progression, which may be caused by the down-regulation of histone acetylase p300 and the upregulation of histone deacetylase I(HDAC I). Ectopic expression of Sema3 E substantially inhibited the proliferation and colony formation of gastric cancer cell lines in vitro and their capacity to develop xenografts in vivo. Propidium iodide staining indicated that Sema3 E restrained G1-S transition in the cell cycle. In addition, Sema3 E was found to promote the apoptosis of gastric cancer cell lines, and in this study, Sema3 E attenuated the migration and invasion abilities of gastric cancer cells in vitro. Furthermore, it was found that the ERK1/2 and Akt signaling pathways,Twist/Ecadherin signaling axis are involved in the inhibitory effect of Sema3 E on gastric cancer cells.Conclusion: Altogether, these data suggests that an imbalance in the epigenetic regulation of gastric cancer results in the silencing of Sema3 E, which in turn contributes to the pathogenesis of gastric cancer. Our results indicated that Sema3 E acted as a candidate tumor suppressor in gastric cancer, which will provide a new clue for gastric cancer therapy clinically. |
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