EZH2 Upregulates Notch Signaling Pathway Genes and Increases Cell Migration in Gastric Cancers

Gastric cancer, faced different therapeutic imperfections such as chemoresistance, dangerous side effects, and non-specificity of the treatments. Our aim in the present study was to investigate the potential of the Enhancer of Zeste Homolog 2 (EZH2) gene as a therapeutic target through analyzing its role in cell migration and regulation of Notch signaling pathway in gastric cancer. The overexpression and silencing studies of EZH2 gene were performed in MKN-45 and AGS gastric cancer cell lines using pCMV3-ORF-HA and RNAi-Ready pSIREN-RetroQ Retroviral vectors, respectively. The cell migration was assessed using wound healing and closure assays. The effect of EZH2 overexpression and silencing on the Notch signaling pathway was evaluated using real-time PCR. The EZH2 expression was directly correlated with the increased rate of cell migration. Furthermore, EZH2 increased expression of the majority of the Notch signaling pathway genes including MAML1, HES5, NOTCH1, NOTCH2, NOTCH3, HEY1, and HES1 in MKN-45 and AGS cells. EZH2, as an upstream regulator, enhances the cell migration capacity and modulate expression of Notch signaling pathway gene in gastric cancer. EZH2 may be considered as a proper target for the treatment of gastric cancer.