The activity of Wnt/β-catenin, in the present research, was initially blocked by miR-149 mimic but then recovered upon RNF2 overexpression, indicating that the RNF2-Wnt/β-catenin cascade was accountable for the development of ESCC after miR-149 downregulation. The gene discussed is RNF2; the disease is esophageal squamous cell carcinoma.