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). The gene discussed is CBFB; the disease is gastric cancer.