Top

Published in:

01-06-2013 | Research Article

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

Authors: Chi-Chih Lai, Pai-Mei Lin, Sheng-Fung Lin, Cheng-Hsien Hsu, Hsin-Ching Lin, Ming-Luen Hu, Cheng-Ming Hsu, Ming-Yu Yang

Published in: Tumor Biology | Issue 3/2013

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.

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.PubMedCrossRef

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

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.CrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

10.

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

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

16.

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

17.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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

Title: Altered expression of SIRT gene family in head and neck squamous cell carcinoma
Authors: Chi-Chih Lai
Pai-Mei Lin
Sheng-Fung Lin
Cheng-Hsien Hsu
Hsin-Ching Lin
Ming-Luen Hu
Cheng-Ming Hsu
Ming-Yu Yang
Publication date: 01-06-2013
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 3/2013
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-0726-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2013

MicroRNA-31-5p modulates cell cycle by targeting human mutL homolog 1 in human cancer cells

Expression of UbcH10 in pancreatic ductal adenocarcinoma and its correlation with prognosis

Concurrent chemoradiotherapy with or without adjuvant chemotherapy in intermediate and locoregionally advanced nasopharyngeal carcinoma

Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC

Colorectal cancer: a researcher’s perspective of the molecular angel’s gone eccentric in the Vale of Kashmir

Overexpression of microRNA-21 regulating PDCD4 during tumorigenesis of liver fluke-associated cholangiocarcinoma contributes to tumor growth and metastasis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer