Zinc Finger Protein 479 Promotes Metastasis and Epithelial-Mesenchymal Transition in Gastric Cancer via MEK/ERK/DNMT1 Signaling Pathway

Abstract

The carcinogenic function of zinc finger protein 479 (ZNF479) has been found in a few sorts of cancer. However, the part of ZNF479 in gastric cancer remains vague. In this study, the effect of ZNF479 on gastric cancer cell survival, metastasis and epithelial mesenchymal transition (EMT) was investigated using the Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. Immunofluorescence assay and Western blot was carried out to evaluate the levels of cell cycle, EMT, and MEK/ERK/DNMT1 pathway-related proteins. A lung metastasis cancer mice model was constructed to evaluate the function of ZNF479 on tumor metastasis in vivo. We noticed that overexpression of ZNF479 promoted cell growth, cell cycle progression, invasion and EMT of gastric cancer cells, whereas ZNF479 knockdown appeared the inverse comes about. Moreover, downregulation of ZNF479 hindered tumor metastasis in mice. Advanced investigation implied that ZNF479 was engaged in the regulation of gastric cancer progression by affecting the MEK/ERK/DNMT1 pathway for that the MEK-specific inhibitor PD98059 reversed the impact of ZNF479 overexpression on gastric cancer cells and repressed MEK/ERK/DNMT1 signal. In conclusion, ZNF479 promotes gastric cancer cells by activating the MEK/ERK/DNMT1 pathway, ZNF479 may give a new and viable gene target for gastric cancer intercession.