PloS one, 2016-11, Vol.11 (11), p.e0165835-e0165835
2016
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Details
- Autor(en) / Beteiligte
- Titel
- SIRT6 Depletion Suppresses Tumor Growth by Promoting Cellular Senescence Induced by DNA Damage in HCC
- Ist Teil von
- PloS one, 2016-11, Vol.11 (11), p.e0165835-e0165835
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The role of Sirtuin 6 (SIRT6) as a tumor suppressor or oncogene in liver cancer remains controversial. Thus, we identified the specific role of SIRT6 in the progression of hepatocellular carcinoma (HCC). SIRT6 expression was significantly higher in HCC cell lines and HCC tissues from 138 patients than in an immortalized hepatocyte cell line, THLE-2 and non-tumor tissues, respectively. SIRT6 knockdown by shRNA suppressed the growth of HCC cells and inhibited HCC tumor growth in vivo. In addition, SIRT6 silencing significantly prevented the growth of HCC cell lines by inducing cellular senescence in the p16/Rb- and p53/p21-pathway independent manners. Microarray analysis revealed that the expression of genes involved in nucleosome assembly was apparently altered in SIRT6-depleted Hep3B cells. SIRT6 knockdown promoted G2/M phase arrest and downregulation of genes encoding histone variants associated with nucleosome assembly, which could be attributed to DNA damage. Taken together, our findings suggest that SIRT6 acts as a tumor promoter by preventing DNA damage and cellular senescence, indicating that SIRT6 represents a potential therapeutic target for the treatment of HCC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0165835Titel-ID: cdi_plos_journals_1837231550
- Format
- –
- Schlagworte
- Analysis, Animals, Apoptosis, Assembly, Biology and life sciences, Biotechnology, Breast cancer, Cancer genetics, Cancer treatment, Carcinoma, Hepatocellular - metabolism, Carcinoma, Hepatocellular - physiopathology, Cell cycle, Cell Line, Tumor, Cellular Senescence - physiology, Cyclin-dependent kinases, Damage prevention, Deoxyribonucleic acid, DNA, DNA damage, DNA Damage - physiology, DNA microarrays, DNA repair, Gene expression, Gene Expression Regulation, Neoplastic - physiology, Gene Knockdown Techniques, Genes, Growth, Growth factors, Hepatocellular carcinoma, Humans, Kinases, Life sciences, Liver, Liver cancer, Liver Neoplasms - metabolism, Liver Neoplasms - physiopathology, Male, Medicine and Health Sciences, Metabolism, Mice, Mice, Nude, Neoplasm Transplantation, Oligonucleotide Array Sequence Analysis, p53 Protein, Pancreatic cancer, Research and Analysis Methods, Rodents, Senescence, Sirtuins - deficiency, Sirtuins - physiology, Tissues, Tumor suppressor genes