Elsevier

Translational Oncology

Volume 10, Issue 6, December 2017, Pages 917-927
Translational Oncology

Downregulation of SIRT2 Inhibits Invasion of Hepatocellular Carcinoma by Inhibiting Energy Metabolism1

https://doi.org/10.1016/j.tranon.2017.09.006Get rights and content
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Abstract

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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1

Grant support: This work was supported by grants from the National Natural Science Foundation of China (No. 81602076), the Jiangsu Clinical Medical Center of Digestive Disease (BL2012001), the Natural Science Foundation from the Department of Science & Technology of Jiangsu Province (BK20160113) and the Fundamental Research Funds for the Central Universities (No. 021414380244).

2

These authors contribute equally to this work.