SI RT6 is an important histone modifying protein that regulates DNA repair,telomere maintenance,energy me-tabolism,and target gene expression.Recently SIRT6 has been identifi ed as a tumor suppressor and is down-regulated in certain cancer types,but not in other can-cers.From deposited gene profi ling studies we found that SIRT6 was overexpressed in prostate tumors,compared with normal or paratumor prostate tissues.Tissue micro-array studies confi rmed the higher levels of SIRT6 in both prostate tumor tissues and prostate cancer cells than in their normal counterparts.Knockdown of SIRT6 in human prostate cancer cells led to sub-G1 phase arrest of cell cy-cle,increased apoptosis,elevated DNA damage level and decrease in BCL2 gene expression.Moreover,SIRT6-de-fi ciency reduced cell viability and enhanced chemothera-peutics sensitivity.Taken together,this study provides the fi rst evidence of SIRT6 overexpression in human prostate cancer,and SIRT6 regulation could be exploited for pros-tate cancer therapy.