Mechanistically, miR-558 recognizes its complementary site within HPSE promoter to decrease the binding of Smad4 in an Argonaute 1 (AGO1)-dependent manner, thus facilitating the in vitro and in vivo tumorigenesis and progression of gastric cancer cells, indicating the oncogenic functions of miR-558 in gastric cancer. This evidence concerns the gene AGO1 and gastric cancer.