Our results provide a molecular mechanism for the hypoxia-induced inhibition of RUNX3, which can enhance survival/proliferation of gastric cancer cells and suppressing their apoptosis during early tumorigenesis (Fig. 7F): hypoxia induces G9a that methylates RUNX3 at K129/K171, inducing cytosolic localization of RUNX3 via dissociating with importin-α7 (1) and the methylation decreases the binding of RUNX3 to the promoter of target genes (3) by inhibiting interactions of RUNX3 with CBFβ and p300 (2). This evidence concerns the gene RUNX3 and gastric cancer.