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Altered expression of SIRT gene family in head and neck squamous cell carcinoma

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Tumor Biology

Abstract

Head and neck squamous cell carcinoma (HNSCC) include a group of malignant neoplasms that arise from the upper aerodigestive tract and represent the seventh most common cause of cancer-related death. The overall 5-year survival rates have not significantly improved for decades in spite of the advances in the field of oncology and surgery, encouraging further research on factors that might modify disease prognosis. The silent information regulator (SIR) genes (Sirtuins) play key roles in cellular stress and are associated with aging-related diseases including cancer. Currently, seven human sirtuin (SIRT1–7) genes have been identified, but the roles of SIRT genes in HNSCC are still uncertain. Therefore, in this study, we used real-time quantitative reverse transcription-polymerase chain reaction to investigate the expressions of the seven SIRT genes in human HNSCC tissues to assess the changes in cancerous and noncancerous parts and the correlation with different tumor behaviors. Our results demonstrated that the expression levels of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly downregulated in cancerous tissues compared with noncancerous tissues (all p < 0.01). The expression levels of SIRT1, SIRT2, SIRT3, SIRT5, and SIRT7 showed downregulation in advanced stages in respect to early stages (p < 0.05). These results indicate that the downregulation of SIRT genes expression may contribute to the development of cancer and trigger the neoplastic disease to more advanced stages. Our study indicates that SIRT genes expression could help in the diagnosis and represent a prognostic biomarker in HNSCC.

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References

  1. Mehanna H, Paleri V, West CM, Nutting C. Head and neck cancer-part 1: epidemiology, presentation, and preservation. Clin Otolaryngol. 2011;36(1):65–8. doi:10.1111/j.1749-4486.2010.02231.x.

    Article  PubMed  CAS  Google Scholar 

  2. Department of Health, EY T, R.O.C. Cancer registry annual report in Taiwan area, 2011. University of Arizona, 2012.

  3. Hashibe M, Brennan P, Benhamou S, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Instr. 2007;99(10):777–89. doi:10.1093/jnci/djk179.

    Article  Google Scholar 

  4. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301. doi:10.1200/JCO.2011.36.4596.

    Article  PubMed  Google Scholar 

  5. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. doi:10.1056/NEJMoa0912217.

    Article  PubMed  CAS  Google Scholar 

  6. Goldenberg D, Lee J, Koch WM, et al. Habitual risk factors for head and neck cancer. Otolaryngol Head Neck Surg. 2004;131(6):986–93. doi:10.1016/j.otohns.2004.02.035.

    Article  PubMed  Google Scholar 

  7. Chien YC, Chen JY, Liu MY, et al. Serologic markers of Epstein–Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med. 2001;345(26):1877–82. doi:10.1056/NEJMoa011610.

    Article  PubMed  CAS  Google Scholar 

  8. Massano J, Regateiro FS, Januario G, Ferreira A. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(1):67–76. doi:10.1016/j.tripleo.2005.07.038.

    Article  PubMed  Google Scholar 

  9. Haigis MC, Guarente LP. Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006;20(21):2913–21. doi:10.1101/gad.1467506.

    Article  PubMed  CAS  Google Scholar 

  10. Schumacker PT. A tumor suppressor SIRTainty. Cancer Cell. 2010;17(1):5–6. doi:10.1016/j.ccr.2009.12.032.

    Article  PubMed  CAS  Google Scholar 

  11. Albani D, Polito L, Forloni G. Sirtuins as novel targets for Alzheimer's disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis. 2010;19(1):11–26. doi:10.3233/JAD-2010-1215.

    PubMed  Google Scholar 

  12. Esteves AR, Lu J, Rodova M, et al. Mitochondrial respiration and respiration-associated proteins in cell lines created through Parkinson's subject mitochondrial transfer. J Neurochem. 2010;113(3):674–82. doi:10.1111/j.1471-4159.2010.06631.x.

    Article  PubMed  CAS  Google Scholar 

  13. Avogaro A, de Kreutzenberg SV, Fadini GP. Insulin signaling and life span. Pflugers Arch. 2010;459(2):301–14. doi:10.1007/s00424-009-0721-8.

    Article  PubMed  CAS  Google Scholar 

  14. Ota H, Eto M, Ogawa S, Iijima K, Akishita M, Ouchi Y. SIRT1/eNOS axis as a potential target against vascular senescence, dysfunction and atherosclerosis. J Atheroscler Thromb. 2010;17(5):431–5.

    Article  PubMed  CAS  Google Scholar 

  15. Voelter-Mahlknecht S, Mahlknecht U. The sirtuins in the pathogenesis of cancer. Clin Epigenetics. 2010;1(3–4):71–83. doi:10.1007/s13148-010-0008-0.

    Article  PubMed  CAS  Google Scholar 

  16. Bosch-Presegue L, Vaquero A. The dual role of sirtuins in cancer. Genes Cancer. 2011;2(6):648–62. doi:10.1177/1947601911417862.

    Article  PubMed  CAS  Google Scholar 

  17. Deng CX. SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci. 2009;5(2):147–52.

    Article  PubMed  CAS  Google Scholar 

  18. Asher G, Gatfield D, Stratmann M, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134(2):317–28. doi:10.1016/j.cell.2008.06.050.

    Article  PubMed  CAS  Google Scholar 

  19. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009;324(5927):654–7. doi:10.1126/science.1170803.

    Article  PubMed  CAS  Google Scholar 

  20. Belden WJ, Dunlap JC. SIRT1 is a circadian deacetylase for core clock components. Cell. 2008;134(2):212–4. doi:10.1016/j.cell.2008.07.010.

    Article  PubMed  CAS  Google Scholar 

  21. Hsu CM, Lin SF, Lu CT, Lin PM, Yang MY. Altered expression of circadian clock genes in head and neck squamous cell carcinoma. Tumour Biol. 2012;33(1):149–55. doi:10.1007/s13277-011-0258-2.

    Article  PubMed  CAS  Google Scholar 

  22. Pazienza V, Piepoli A, Panza A, et al. SIRT1 and the clock gene machinery in colorectal cancer. Cancer Invest. 2012;30(2):98–105. doi:10.3109/07357907.2011.640650.

    Article  PubMed  CAS  Google Scholar 

  23. Ashraf N, Zino S, Macintyre A, et al. Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer. 2006;95(8):1056–61. doi:10.1038/sj.bjc.6603384.

    Article  PubMed  CAS  Google Scholar 

  24. Kim HS, Patel K, Muldoon-Jacobs K, et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell. 2010;17(1):41–52. doi:10.1016/j.ccr.2009.11.023.

    Article  PubMed  CAS  Google Scholar 

  25. Finley LW, Carracedo A, Lee J, et al. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell. 2011;19(3):416–28. doi:10.1016/j.ccr.2011.02.014.

    Article  PubMed  CAS  Google Scholar 

  26. Alhazzazi TY, Kamarajan P, Joo N, et al. Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer. Cancer. 2011;117(8):1670–8. doi:10.1002/cncr.25676.

    Article  PubMed  CAS  Google Scholar 

  27. Hiratsuka M, Inoue T, Toda T, et al. Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem Biophys Res Commun. 2003;309(3):558–66.

    Article  PubMed  CAS  Google Scholar 

  28. Mahlknecht U, Ho AD, Letzel S, Voelter-Mahlknecht S. Assignment of the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome band 6p23 by in situ hybridization. Cytogenet Genome Res. 2006;112(3–4):208–12. doi:10.1159/000089872.

    Article  PubMed  CAS  Google Scholar 

  29. Ouaissi M, Sielezneff I, Silvestre R, et al. High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas. Ann Surg Oncol. 2008;15(8):2318–28. doi:10.1245/s10434-008-9940-z.

    Article  PubMed  Google Scholar 

  30. Ma W, Stafford LJ, Li D, et al. GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. J Cell Biochem. 2007;100(6):1376–86. doi:10.1002/jcb.21140.

    Article  PubMed  CAS  Google Scholar 

  31. Michishita E, McCord RA, Berber E, et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature. 2008;452(7186):492–6. doi:10.1038/nature06736.

    Article  PubMed  CAS  Google Scholar 

  32. Mostoslavsky R, Chua KF, Lombard DB, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006;124(2):315–29. doi:10.1016/j.cell.2005.11.044.

    Article  PubMed  CAS  Google Scholar 

  33. Garzino-Demo P, Dell'Acqua A, Dalmasso P, et al. Clinicopathological parameters and outcome of 245 patients operated for oral squamous cell carcinoma. J Craniomaxillofac Surg. 2006;34(6):344–50. doi:10.1016/j.jcms.2006.04.004.

    Article  PubMed  Google Scholar 

  34. Le Tourneau C, Jung GM, Borel C, Bronner G, Flesch H, Velten M. Prognostic factors of survival in head and neck cancer patients treated with surgery and postoperative radiation therapy. Acta Otolaryngol. 2008;128(6):706–12. doi:10.1080/00016480701675668.

    Article  PubMed  Google Scholar 

  35. Larsen SR, Johansen J, Sorensen JA, Krogdahl A. The prognostic significance of histological features in oral squamous cell carcinoma. J Oral Pathol Med. 2009;38(8):657–62. doi:10.1111/j.1600-0714.2009.00797.x.

    Article  PubMed  CAS  Google Scholar 

  36. Woolgar JA. Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. Oral Oncol. 2006;42(3):229–39. doi:10.1016/j.oraloncology.2005.05.008.

    Article  PubMed  Google Scholar 

  37. Cojocariu OM, Huguet F, Lefevre M, Perie S. Prognosis and predictive factors in head-and-neck cancers. Bull Cancer. 2009;96(4):369–78. doi:10.1684/bdc.2009.0777.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was partly supported by grants from the National Science Council of Taiwan (NSC 100-2314-B-037-031, NSC 100-2314-B-182A-023, and NSC 101-2314-B-182A-051), Chang Gung Memorial Hospital (CMRPG8B0361 and CMRPD8A0491), and Kaohsiung Medical University Hospital (99–23).

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Authors and Affiliations

  1. Division of Laryngology, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Da-Pi Rd., Niaosong District, 833 Kaohsiung City, Taiwan

    Chi-Chih Lai, Hsin-Ching Lin & Cheng-Ming Hsu

  2. Department of Nursing, I-Shou University, Kaohsiung County, Taiwan

    Pai-Mei Lin

  3. Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan

    Sheng-Fung Lin

  4. Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan

    Sheng-Fung Lin

  5. School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Cheng-Hsien Hsu

  6. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Ming-Luen Hu

  7. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, 333 Tao-Yuan, Taiwan

    Cheng-Ming Hsu & Ming-Yu Yang

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  1. Chi-Chih Lai
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Correspondence to Cheng-Ming Hsu or Ming-Yu Yang.

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Lai, CC., Lin, PM., Lin, SF. et al. Altered expression of SIRT gene family in head and neck squamous cell carcinoma. Tumor Biol. 34, 1847–1854 (2013). https://doi.org/10.1007/s13277-013-0726-y

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  • DOI: https://doi.org/10.1007/s13277-013-0726-y

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