STAT3 and gastric cancer: SIRT1 is upregulated in GC tissues and SIRT1 depletion promotes GC progression through activation of STAT3/MMP-13 signaling.331 SIRT4 and SIRT6 are downregulated in GC tissues, and their low expression is negatively correlated with tumor size and pathological grade, which predicts poor prognosis.383,453 Mechanistically, SIRT4 inhibits cell proliferation, migration, and invasion in GC via regulating EMT.