title: SIRT1 promotes metastasis of human osteosarcoma cells.
abstract: Pulmonary metastasis is the leading cause of mortality in patients with osteosarcoma; however, the underlying mechanism remains unclear. The NAD+-dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in carcinogenesis through deacetylation of important regulatory proteins. Here, we report that SIRT1 promotes osteosarcoma metastasis by regulating the expression of metastatic-associated genes. The SIRT1 protein was significantly upregulated in most primary osteosarcoma tumours, compared with normal tissues, and the SIRT1 expression level may be coupled with metastatic risk in patients with osteosarcoma. Moreover, the results of cell migration and wound-healing assays further suggested that higher expression of SIRT1 promoted invasive activity of osteosarcoma cells. Importantly, downregulating SIRT1 with shRNA inhibited the migration ability of osteosarcoma cells in vitro and suppressed tumour lung metastasis in mice. Finally, a gene expression analysis showed that knockdown of SIRT1 profoundly activated translation of its downstream pathway, particularly at migration and invasion. In summary, high levels of SIRT1 may be a biomarker for a high metastatic rate in osteosarcoma patients; inhibiting SIRT1 could be a potent therapeutic intervention for these patients.
authors: Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, P.R. China.
authors: Ning
authors: N
authors: Zhang
authors: Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, P.R. China.
authors: Tao
authors: T
authors: Xie
authors: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors: Miao
authors: M
authors: Xian
authors: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors: Yi-Jie
authors: YJ
authors: Wang
authors: Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, P.R. China.
authors: Heng-Yuan
authors: HY
authors: Li
authors: Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors: Mei-Dan
authors: MD
authors: Ying
authors: Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, P.R. China.
authors: Zhao-Ming
authors: ZM
authors: Ye
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics / Q000556:secondary*; D034622:RNA Interference; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: SIRT1; biomarker; invasion; metastasis; osteosarcoma