Gao Yi, Qu Yuxing, Zhou Qi, Ma Yong
Department of Orthopedics and Traumatology, First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.
Department of Orthopedics, Changzhou City Hospital of Traditional Chinese Medicine, Changzhou, Jiangsu 213000, P.R. China.
Oncol Lett. 2019 Jan;17(1):1237-1244. doi: 10.3892/ol.2018.9676. Epub 2018 Nov 8.
SIRT6, is a member of the NAD-dependent sirtuin family of enzymes, and has been reported as a novel tumor suppressor gene or oncogene, dependent on the type of cancer. However, the role of SIRT6 in osteosarcoma has not been investigated. The present study demonstrated that the expression of SIRT6 was downregulated in osteosarcoma tissues and osteosarcoma cell lines when compared with adjacent tissues or osteoblastic cell lines. Kaplan-Meier analysis was performed to evaluate the prognostic significance of SIRT6. The overall survival of patients with higher expression of SIRT6 was significantly longer than patients with lower expression. Subsequently, MTT and invasion assays were performed to detect the biological functions of SIRT6 in osteosarcoma cells . The results revealed that overexpression of SIRT6 inhibited SAOS-2 and MG-63 cell proliferation and invasion. Knockdown of SIRT6 enhanced cell ability for the proliferation and invasion. A qChIP assay, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blotting confirmed that CDH2 (N-cadherin) was a target of SIRT6. SIRT6 overexpression suppressed N-cadherin on the mRNA and protein levels. In addition, it was confirmed that the promotional effect of Si-SIRT6 on OS cell growth and invasion was suppressed by downregulating N-cadherin. The present study suggested that SIRT6 may serve as a tumor suppressor during the development of osteosarcoma. In addition, N-cadherin may be a promising therapeutic target for osteosarcoma.
SIRT6是烟酰胺腺嘌呤二核苷酸（NAD）依赖性sirtuin家族酶的成员，根据癌症类型的不同，它被报道为一种新型肿瘤抑制基因或癌基因。然而，SIRT6在骨肉瘤中的作用尚未得到研究。本研究表明，与相邻组织或成骨细胞系相比，骨肉瘤组织和骨肉瘤细胞系中SIRT6的表达下调。采用Kaplan-Meier分析评估SIRT6的预后意义。SIRT6高表达患者的总生存期明显长于低表达患者。随后，进行MTT和侵袭试验以检测SIRT6在骨肉瘤细胞中的生物学功能。结果显示，SIRT6过表达抑制了SAOS-2和MG-63细胞的增殖和侵袭。敲低SIRT6增强了细胞的增殖和侵袭能力。染色质免疫沉淀定量分析（qChIP）、荧光素酶报告基因分析、逆转录定量聚合酶链反应和蛋白质印迹证实，CDH2（N-钙黏蛋白）是SIRT6的一个靶点。SIRT6过表达在mRNA和蛋白质水平上抑制了N-钙黏蛋白。此外，证实下调N-钙黏蛋白可抑制Si-SIRT6对骨肉瘤细胞生长和侵袭的促进作用。本研究表明，SIRT6在骨肉瘤发生发展过程中可能作为一种肿瘤抑制因子。此外，N-钙黏蛋白可能是骨肉瘤一个有前景的治疗靶点。
