RUNX3 inhibits survivin expression and induces cell apoptosis in gastric cancer

Transcription factor RUNX3 is associated with gastric tumorigenesis and progression through regulating the expression of its target genes. Survivin is a member of the inhibitor of apoptosis (IAP) family and has been shown to inhibit cell apoptosis and promote cell proliferation. Increased survivin expression has been found in various cancer types, including gastric cancer. In this study, we found that restoration of RUNX3 promotes cell apoptosis through inhibiting the survivin expression, while RUNX3 inhibition increases the expression of survivin in gastric cancer cell lines. Moreover, RUNX3 over-expression inhibits,whereas its inhibition increases, the promoter activity of survivin gene, respectively. RUNX3-R122C, a mutation located in the conserved Runt domain, has no effect on the promoter activity of survivin gene. We further identified a RUNX3-binding site in the promoter of survivin gene and the binding of RUNX3 on survivin promoter leads to significantly inhibition of survivin expression. Finally, we confirmed the negative correlation of RUNX3 and survivin expression in clinical specimens of gastric cancer. These findings reveal a novel mechanism of RUNX3 for the induction of cell apoptosis in human gastric cancer.