Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients.
Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients.
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DOI：
10.1371/journal.pone.0124670
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Montuenga LM
中科院分区：
文献类型：
--
作者：
Grbesa I;Pajares MJ;Martínez-Terroba E;Agorreta J;Mikecin AM;Larráyoz M;Idoate MA;Gall-Troselj K;Pio R;Montuenga LM
Sirtuin 1（SIRT 1）和sirtuin 2（SIRT 2）是NAD+依赖性蛋白脱乙酰酶，参与调节关键的癌症相关基因。在这项研究中，我们评估了这些脱乙酰酶在肺癌生物学中的相关性。在来自105名患者的非小细胞肺癌（NSCLC）细胞系和原发性肿瘤中测定SIRT 1和SIRT 2的蛋白水平。使用siRNA介导的技术或tenovin-1（一种SIRT 1和SIRT 2抑制剂）评估肺癌细胞系中SIRT 1和SIRT 2下调后增殖的变化。与非肿瘤肺上皮细胞相比，在NSCLC细胞系中发现高SIRT 1和SIRT 2蛋白水平。SIRT 1和SIRT 2蛋白在肺原发性肿瘤中的表达也显著高于正常组织（两种sirtuins均P<0.001）。在腺癌中观察到比鳞状细胞癌更强的核SIRT 1染色（P=0.033）。有趣的是，在NSCLC患者中，高SIRT 1和SIRT 2表达水平与较短的无复发生存期相关（分别为P=0.04和P=0.007）。此外，SIRT 1和SIRT 2高表达的组合是较短的无复发生存期（P=0.002）和总生存期（P=0.022）的独立预后因素。体外研究表明，SIRT 1和/或SIRT 2下调显著降低NSCLC的增殖。我们的研究结果支持SIRT 1和SIRT 2在肺癌中具有促肿瘤作用，促进细胞增殖的假设。此外，这些蛋白的表达与NSCLC患者的不良预后相关，并可能有助于识别那些具有高复发风险的NSCLC患者，这些患者可以从切除术后的辅助治疗中获益。
Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biology. Protein levels of SIRT1 and SIRT2 were determined in non-small cell lung cancer (NSCLC) cell lines and primary tumors from 105 patients. Changes in proliferation were assessed after SIRT1 and SIRT2 downregulation in lung cancer cell lines using siRNA-mediated technology or tenovin-1, a SIRT1 and SIRT2 inhibitor. High SIRT1 and SIRT2 protein levels were found in NSCLC cell lines compared with non-tumor lung epithelial cells. The expression of SIRT1 and SIRT2 proteins was also significantly higher in lung primary tumors than in normal tissue (P<0.001 for both sirtuins). Stronger nuclear SIRT1 staining was observed in adenocarcinomas than in squamous cell carcinomas (P=0.033). Interestingly, in NSCLC patients, high SIRT1 and SIRT2 expression levels were associated with shorter recurrence-free survival (P=0.04 and P=0.007, respectively). Moreover, the combination of high SIRT1 and SIRT2 expression was an independent prognostic factor for shorter recurrence-free survival (P=0.002) and overall survival (P=0.022). In vitro studies showed that SIRT1 and/or SIRT2 downregulation significantly decreased proliferation of NSCLC. Our results support the hypothesis that SIRT1 and SIRT2 have a protumorigenic role in lung cancer, promoting cell proliferation. Moreover, the expression of these proteins is associated with poor prognosis in NSCLC patients and may help to identify those NSCLC patients with high risk of recurrence that could benefit from adjuvant therapy after resection.
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影响因子：
4.8
作者：
Hoffmann, Gesine;Breitenbuecher, Frank;Ehrenhofer-Murray, Ann E.
通讯作者：
Ehrenhofer-Murray, Ann E.
DOI：
10.1073/pnas.0911325107
发表时间：
2010-05-18
影响因子：
11.1
作者：
Holloway, Kimberly R.;Calhoun, Tara N.;Pruitt, Kevin
通讯作者：
Pruitt, Kevin
影响因子：
16
作者：
Avalos, JL;Celic, I;Wolberger, C
通讯作者：
Wolberger, C
影响因子：
3.7
作者：
Jang KY;Noh SJ;Lehwald N;Tao GZ;Bellovin DI;Park HS;Moon WS;Felsher DW;Sylvester KG
通讯作者：
Sylvester KG
影响因子：
3.7
作者：
Hirai S;Endo S;Saito R;Hirose M;Ueno T;Suzuki H;Yamato K;Abei M;Hyodo I
通讯作者：
Hyodo I