Sirt6 suppresses hepatocellular carcinoma cell growth via inhibiting the extracellular signal-regulated kinase signaling pathway
| Autor: | Zhi-Gao Zhang, Cheng-Yong Qin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Down-Regulation Apoptosis Biology Biochemistry Nitriles Butadienes Genetics Extracellular Humans Sirtuins Phosphorylation RNA Small Interfering Autocrine signalling Molecular Biology Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Caspase 3 Kinase Liver Neoplasms Hep G2 Cells Cell cycle digestive system diseases Cell biology HEK293 Cells Oncology Cell culture Cancer research Molecular Medicine Cyclin-dependent kinase 8 RNA Interference Signal transduction Reactive Oxygen Species A431 cells Signal Transduction |
| Zdroj: | Molecular Medicine Reports. 9:882-888 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2013.1879 |
| Popis: | Sirt6, a member of the mammalian sirtuin family, is a protein that is located in the nucleus and is an NAD+‑dependent deacetylase important in the control of metabolic activity and genome stability. Recently, several studies have demonstrated the potential role of Sirt6 in tumor biology; however, the role of Sirt6 in hepatocellular carcinoma (HCC) remains unclear. In the present study, Sirt6 protein expression was found to be downregulated in human HCC tissue compared with adjacent normal tissue. Knockdown of Sirt6 promoted growth of the HepG2 HCC cell line, whereas overexpression of Sirt6 inhibited the growth of HepG2 cells. Overexpression of Sirt6 induced apoptosis in HepG2 cells, which was demonstrated by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay and cleaved caspase-3 immunoblotting. Furthermore, overexpression of Sirt6 decreased intracellular reactive oxygen species and superoxide anion levels. Finally, overexpression of Sirt6 inhibited phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), and blocking the ERK1/2 pathway with chemical-specific inhibitor U0126, attenuated the tumor suppressive effect of overexpression of Sirt6. Collectively, these data suggest that Sirt6 is a tumor suppressor in HCC cells and may be a promising therapeutic target in HCC. |
| Databáze: | OpenAIRE |
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