Downregulation of SIRT2 Inhibits Invasion of Hepatocellular Carcinoma by Inhibiting Energy Metabolism.
Downregulation of SIRT2 Inhibits Invasion of Hepatocellular Carcinoma by Inhibiting Energy Metabolism.
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SIRT2 下调通过抑制能量代谢抑制肝细胞癌的侵袭
DOI：
10.1016/j.tranon.2017.09.006
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发表时间：
2017-12
影响因子：
5
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Huang S;Zhao Z;Tang D;Zhou Q;Li Y;Zhou L;Yin Y;Wang Y;Pan Y;Dorfman RG;Ling T;Zhang M
肝细胞癌（HCC）是最常见的肿瘤之一，转移是HCC相关死亡的最重要特征。越来越多的证据表明SIRT2（一种组蛋白去乙酰化酶）在癌细胞中具有动态调节作用。不幸的是，SIRT2在HCC中的作用及其抑制的抗肿瘤活性尚不清楚。本研究旨在评估SIRT2在HCC中的生物学功能，确定SIRT2的靶点，评估其治疗效果。我们发现，与邻近正常组织相比，HCC组织中SIRT2表达上调，这与患者生存率降低有关。虽然CCK8和集落形成实验显示SIRT2抑制略微促进HCC细胞系的增殖，但SIRT2敲低会减少HCC细胞的侵袭。我们证明SIRT2的下调可以抑制其下游靶点磷酸烯醇丙酮酸羧激酶1和谷氨酰胺酶，这与线粒体代谢和E-Cadherin途径有关。这些结果首次表明，下调SIRT2可减少人类HCC细胞的迁移和侵袭，表明抑制SIRT2可能是治疗HCC的有效治疗策略。
Hepatocellular carcinoma (HCC) is one of the most common neoplasms, and metastasis is the most important feature for HCC-related deaths. Mounting evidence implies the dynamic regulatory role of SIRT2, a histone deacetylase, in cancer cells. Unfortunately, the role of SIRT2 and the antitumor activity of its inhibition are not known in HCC. The present study aims to evaluate the biological function of SIRT2 in HCC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Although CCK8 and colony-formation assays showed that SIRT2 inhibiton marginally promotes proliferation in HCC cell lines, SIRT2 knockdown decreased the invasion of HCC cells. We demonstrated that downregulation of SIRT2 could inhibit its downstream target phosphoenolpyruvate carboxykinase 1 and glutaminase, which is related to mitochondrial metabolism and the E-Cadherin pathway. These results demonstrate, for the first time that downregulation of SIRT2 decreases migration as well as invasion in human HCC cells, indicating that inhibiting SIRT2 may be an effective therapeutic strategy for treating HCC.
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影响因子：
16
作者：
Montal ED;Dewi R;Bhalla K;Ou L;Hwang BJ;Ropell AE;Gordon C;Liu WJ;DeBerardinis RJ;Sudderth J;Twaddel W;Boros LG;Shroyer KR;Duraisamy S;Drapkin R;Powers RS;Rohde JM;Boxer MB;Wong KK;Girnun GD
通讯作者：
Girnun GD
影响因子：
4.8
作者：
Liszt, G;Ford, E;Guarente, L
通讯作者：
Guarente, L
影响因子：
5.7
作者：
Gross, Matt I.;Demo, Susan D.;Bennett, Mark K.
通讯作者：
Bennett, Mark K.
影响因子：
64.5
作者：
Lin YY;Lu JY;Zhang J;Walter W;Dang W;Wan J;Tao SC;Qian J;Zhao Y;Boeke JD;Berger SL;Zhu H
通讯作者：
Zhu H
影响因子：
8.4
作者：
McGlynn, Liane M.;Zino, Samer;Shiels, Paul G.
通讯作者：
Shiels, Paul G.