Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer
Open accessAbstract
BACKGROUND: Several sirtuin family members (SIRT1‐7), which are evolutionarily conserved NAD‐dependent deacetylases, play an important role in carcinogenesis. However, their role in oral cancer has not yet been investigated. Therefore, the objective of this study was to investigate whether sirtuins play a role in oral cancer carcinogenesis. METHODS: The expression levels of all sirtuins in several oral squamous cell carcinoma (OSCC) cell lines were compared with normal human oral keratinocytes and observed that SIRT3 was highly expressed. Therefore, tissue microarrays were used to evaluate the clinical relevance of this overexpression. SIRT3 down‐regulation in OSCC cell proliferation and survival was investigated and analyzed by using cell‐proliferation and cell‐viability assays. Ionizing radiation and cisplatin were used to investigate whether SIRT3 down‐regulation could increase the sensitivity of OSCC to both treatments. To further assess the in vivo role of SIRT3 in OSCC carcinogenesis, a floor‐of‐mouth oral cancer murine model was used to study the effect of SIRT3 down‐regulation on OSCC tumor growth in immunodeficient mice. RESULTS: The current results demonstrated for the first time that SIRT3 is overexpressed in OSCC in vitro and in vivo compared with other sirtuins. Down‐regulation of SIRT3 inhibited OSCC cell growth and proliferation and increased OSCC cell sensitivity to radiation and cisplatin treatments in vitro. SIRT3 down‐regulation also reduced tumor burden in vivo. CONCLUSIONS: The current investigation revealed a novel role for SIRT3 in oral cancer carcinogenesis as a promoter of cell proliferation and survival, thus implicating SIRT3 as a new potential therapeutic target to treat oral cancer. Cancer 2011. © 2010 American Cancer Society.
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Studies have indicated a role for SIRT3 in mediating tumor survival.
“On the other hand, studies have indicated a role in mediating tumor survival ((Alhazzazi et al. 2011);(Cheng et al. 2013)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Alhazzazi et al. 2011
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References 39 · Cited by 208
- Authors
- Alhazzazi, T. Y., Kamarajan, P., Joo, N., Huang, J., Verdin, E., D'Silva, N. J., & Kapila, Y. L.
- Affiliations
- University of Michigan (US)
- University of California, San Francisco (US)
- Corresponding author
- Kapila, Yvonne L.
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2010-11-29
- Volume
- 117
- Issue
- 8
- Pages
- 1670-1678
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC3117020
- OpenAlex
- W2068289009
- Cited by
- 208
- References
- 39
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 15 · 2022: 12 · 2021: 18 · 2020: 16 · 2019: 11 · 2018: 12 · 2017: 17 · 2016: 17 · 2015: 19 · 2014: 11 · 2013: 23 · 2012: 15
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- U.S. Public Health Service (R01 DEO14429)
- National Institute of Dental and Craniofacial Research (R01DE014429, R56DE014429)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- SIRT3, sirtuins, oral squamous cell carcinoma, NAD+-dependent deacetylase, therapeutic target, cell proliferation, cell survival, radiosensitivity, cisplatin sensitivity, tumor growth
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Cell Survival, Humans, Mice, Nude, Mouth Neoplasms, Radiation Tolerance, Up-Regulation, Cell Line, Tumor, Cell Proliferation, Mice, Sirtuin 3, Molecular Targeted Therapy
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