Downregulation of ECRG4 by DNMT1 promotes EC growth via IRF3/IFN-γ/miR-29b/DNMT1/ECRG4 positive feedback loop

Esophageal carcinoma (EC) is one of the most common malignant tumors in the world. ECRG4 has been recently discovered to be downregulated in EC. However, the mechanism leading to reduced expression of ECRG4 in esophageal cancer remains obscure. Here, we found that ECRG4 expression was significantly downregulated in EC tissues and cell lines. ECRG4 overexpression led to a significant decrease in proliferation in vitro and in vivo. Mechanistically, ECRG4 can activate IRF3/IFN-γ pathway. IFN-γ can promote the expression of miR-29b. MiR-29b reduces the expression of DNMT1. DNMT1 may affect the expression of ECRG4 by affecting the methylation of ECRG4 promoter. These results reveal ECRG4/IRF3/IFN-γ/miR-29b/DNMT1 positive feedback loop in esophageal carcinoma cells, which may become a potential therapeutic target for esophageal carcinoma.