Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics.
10.1007/s13238-013-3054-5
- Author:
Yewei LIU
1
;
Qian Reuben XIE
1
;
Boshi WANG
1
;
Jiaxiang SHAO
1
;
Tingting ZHANG
1
;
Tengyuan LIU
1
;
Gang HUANG
2
;
Weiliang XIA
3
Author Information
1. School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
2. Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. huang2802@163.com.
3. School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China. wlxia@sjtu.edu.cn.
- Publication Type:Journal Article
- Keywords:
SI RT6;
overexpression;
prostate cancer;
therapy
- MeSH:
Apoptosis;
Cell Cycle Checkpoints;
Cell Line, Tumor;
Cell Proliferation;
Cell Survival;
DNA Damage;
Drug Resistance, Neoplasm;
Gene Knockdown Techniques;
Humans;
Male;
Prostatic Neoplasms;
genetics;
pathology;
therapy;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
Sirtuins;
antagonists & inhibitors;
genetics;
metabolism;
Up-Regulation
- From:
Protein & Cell
2013;4(9):702-710
- CountryChina
- Language:English
-
Abstract:
SIRT6 is an important histone modifying protein that regulates DNA repair, telomere maintenance, energy metabolism, and target gene expression. Recently SIRT6 has been identified as a tumor suppressor and is down-regulated in certain cancer types, but not in other cancers. From deposited gene profiling studies we found that SIRT6 was overexpressed in prostate tumors, compared with normal or paratumor prostate tissues. Tissue micro-array studies confirmed 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 cycle, increased apoptosis, elevated DNA damage level and decrease in BCL2 gene expression. Moreover, SIRT6-deficiency reduced cell viability and enhanced chemotherapeutics sensitivity. Taken together, this study provides the first evidence of SIRT6 overexpression in human prostate cancer, and SIRT6 regulation could be exploited for prostate cancer therapy.
