title: Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics.
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.
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.|Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
authors: Yewei
authors: Y
authors: Liu
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Qian Reuben
authors: QR
authors: Xie
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Boshi
authors: B
authors: Wang
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Jiaxiang
authors: J
authors: Shao
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Tingting
authors: T
authors: Zhang
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Tengyuan
authors: T
authors: Liu
authors: Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. huang2802@163.com.
authors: Gang
authors: G
authors: Huang
authors: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China. wlxia@sjtu.edu.cn.|Clinical Stem Cell Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. wlxia@sjtu.edu.cn.
authors: Weiliang
authors: W
authors: Xia
mesh_terms: D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: SI RT6; overexpression; prostate cancer; therapy
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