Higher expression of ANRIL was significantly correlated with a higher TNM stage and tumor size. Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in Trans by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation.