Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
Lung Cancer. 2013 Oct;82(1):9-15. doi: 10.1016/j.lungcan.2013.05.013. Epub 2013 Jul 31.
Seven Sirtuin family members (SIRT1-7), comprising a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases, are key proteins that regulate multiple physiological processes. SIRT2 was recently reported to play an important role in carcinogenesis. However, its role in non-small cell lung cancer (NSCLC) has not yet been investigated. In this study, we analyzed the expression pattern of SIRT2 in NSCLC tissues from clinical patients and in cell lines, and found that SIRT2 was significantly down-regulated at both the mRNA and protein levels in tumor than non-tumor tissues or cells, which were corroborated by the NSCLC tissue microarray results. Overexpression of SIRT2 in A549 and H1299 cells caused cell proliferation inhibition, cell apoptosis induction and cell cycle arrest. Further analysis showed that SIRT2 overexpression increased the ROS (reactive oxygen species) production and p27 levels. Moreover, up-regulation of SIRT2 in NSCLC cells increased the sensitivity to Cisplatin treatment. Taken together, our results implied that down-regulation of SIRT2 was associated with NSCLC, and regulation of SIRT2 might be an important target for NSCLC therapy.
七个 Sirtuin 家族成员（SIRT1-7），包括一个 NAD+-依赖性蛋白去乙酰化酶和 ADP-核糖基转移酶家族，是调节多种生理过程的关键蛋白。SIRT2 最近被报道在致癌作用中发挥重要作用。然而，其在非小细胞肺癌（NSCLC）中的作用尚未得到研究。在这项研究中，我们分析了 SIRT2 在临床患者的 NSCLC 组织和细胞系中的表达模式，发现 SIRT2 在肿瘤组织中的 mRNA 和蛋白水平均明显低于非肿瘤组织或细胞，这与 NSCLC 组织微阵列结果相符。SIRT2 在 A549 和 H1299 细胞中的过表达导致细胞增殖抑制、细胞凋亡诱导和细胞周期停滞。进一步分析表明，SIRT2 过表达增加了 ROS（活性氧）的产生和 p27 的水平。此外，在 NSCLC 细胞中上调 SIRT2 增加了对顺铂治疗的敏感性。总之，我们的研究结果表明 SIRT2 的下调与 NSCLC 相关，调节 SIRT2 可能是非小细胞肺癌治疗的一个重要靶点。
