SIRT1 promotes metastasis of human osteosarcoma cells.
SIRT1 promotes metastasis of human osteosarcoma cells.
复制标题
SIRT1促进人骨肉瘤细胞转移
DOI：
10.18632/oncotarget.12916
复制
发表时间：
2016-11-29
期刊：
影响因子：
--
通讯作者：
Ye ZM
中科院分区：
文献类型：
--
作者：
Zhang N;Xie T;Xian M;Wang YJ;Li HY;Ying MD;Ye ZM
肺转移是骨肉瘤患者死亡的主要原因，然而，其潜在机制仍不清楚。NAD+依赖性去乙酰化酶，sirtuin 1（SIRT 1），已被报道通过重要的调节蛋白的去乙酰化在癌症发生中发挥关键作用。在这里，我们报告SIRT 1通过调节转移相关基因的表达促进骨肉瘤转移。与正常组织相比，SIRT 1蛋白在大多数原发性骨肉瘤肿瘤中显著上调，并且SIRT 1表达水平可能与骨肉瘤患者的转移风险相关。此外，细胞迁移和伤口愈合实验的结果进一步表明，SIRT 1的高表达促进骨肉瘤细胞的侵袭活性。重要的是，用shRNA下调SIRT 1抑制了骨肉瘤细胞在体外的迁移能力，并抑制了小鼠肿瘤的肺转移。最后，基因表达分析表明，SIRT 1的敲低深刻激活了其下游途径的翻译，特别是在迁移和入侵。总之，高水平的SIRT 1可能是骨肉瘤患者高转移率的生物标志物;抑制SIRT 1可能是这些患者的有效治疗干预。
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.