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KMID : 1034820110070040367
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Molecular & Cellular Toxicology
2011 Volume.7 No. 4 p.367 ~ p.374
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Overexpression of SIRT2 contributes tumor cell growth in hepatocellular carcinomas
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Xie Hong Jian
Jung Kwang-Hwa
Nam Suk-Woo
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Abstract
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The mammalian homolog of yeast Sir2 protein is the sirtuin family of histone deacetylases (HDACs), a NAD+-dependent protein deacetylase in humans. Accumulating evidence suggests that sirtuin 2 (SIRT2) co-localizes with the microtubule network and deacetylates α-tubulin, and is involved in various cellular processes including calorie restriction-dependent life span extension, mitotic cell cycle regulation, cellular apoptosis, DNA damage repair, and genomic silencing. However, the underlying mechanisms of action remains poorly understood, especially in hepatocarcinogenesis. Hence in this study, to determine the association between the aberrant expression of SIRT2 and liver cancer development and progression, SIRT2 expression was investigated in ten selected hepatocellular carcinoma (HCC) tissues and matched normal liver tissues, using RT-PCR and Western blot analysis. Next, SIRT2 was disrupted by siRNA-mediated protein knockdown method to investigate the biological role of SIRT2 in hepatocarcinogenesis in Hep3B cells. As a result, we identified that SIRT2 expression was significantly up-regulated in HCC tissues compared to corresponding normal liver tissues. In addition, suppression of SIRT2 caused regression of tumor cell growth and proliferation. We also found that SIRT2 could interact with α-tubulin and regulates the acetylation status of α-tubulin in Hep3B cells. In conclusion, we suggest that SIRT2 is aberrantly regulated in HCCs which may contribute to the mitogenic potential of tumor cells during the development and progression of HCC, and could be a novel molecular target for therapeutic intervention in liver cancer.
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KEYWORD
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SIRT2, Hepatocellular carcinoma, Hep3B cells, Cell growth, α-tubulin
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