Inhibition of ZNF703 alleviates the progression of gastric cancer through inhibition of HDAC activity

Abstract

Abstract Background: ZNF703 is identified as a therapeutic target in a variety of human cancer. Although ZNF703 overexpresses in gastric cancer frequently, the effects and mechanism of ZNF703 in the progression of gastric cancer is unclear. Methods: Therefore, ZNF703, Ki-67 and BCL-2 expression was measured by histology in clinical cases. We used gastric cells line models to explore the role of ZNF703 in vitro. ZNF703 expression intervention was employed to investigate the role of ZNF703 in proliferation and apoptosis. The relationship between ZNF703 intervention and resistance of chemotherapy was analyzed by using oxaliplatin treatment. Results: In this study, we found that ZNF703 expression in the area of gastric cancer was substantially higher than adjacent normal area. Gastric cancer tissue with ZNF703 high expression level substantially increased Ki-67 and BCL-2 expression. Inhibition of ZNF703 attenuated the gastric cancer cell proliferation and induced apoptosis in SGC7901 and BGC823 cells, while overexpression of ZNF703 in GES-1 cells resulted in the reverse effects. ZNF703 might mediate the viability of gastric cancer cells through down-regulation of HDAC1/2. In addition, after transfected with siRNA-ZNF703, down-regulation of TopoII and P-gp was observed in SGC7901 and BGC823 cells. Further, we showed that inhibition of ZNF703 enhanced the resistance to chemotherapy in vitro. Conclusions: Our study demonstrated that in gastric cancer cells, ZNF703 promoted the proliferation, inhibited apoptosis, and improved their resistance to chemotherapy, suggesting it may be a potential target for the gastric cancer.