Role of SIRT3 in the regulation of redox balance during oral carcinogenesis

I. Chieh Chen, Wei Fan Chiang, Shyun Yeu Liu, Pei Fen Chen, Hung Che Chiang

研究成果: 雜誌貢獻文章

12 引文 斯高帕斯(Scopus)

摘要

Background: Sirtuins (SIRT1-7) are a family of NAD-dependent deacetylases, which play an important role in regulating cancer tumorigenesis; however, their role in oral cancer has been controversial. SIRT3 is localized in the mitochondria, where it deacetylates and activates several enzymes involved in cellular redox balance and defense against oxidative damage.Results: We found that compared with normal human oral keratinocytes (HOK), SIRT3 is highly expressed in oral squamous cell carcinoma (OSCC) cell lines, but the enzymatic deacetylation is significantly reduced. We also sequenced the entire coding region of SIRT3 and found the same mutation in 2 different OSCC cell lines. This point mutation is located in close proximity to the active site of deacetylase in the SIRT3 protein, and reduces the overall enzymatic efficiency of deacetylation. Furthermore, up-regulation of SIRT3 inhibited the cell growth of OSCCs and decreased the levels of basal reactive oxygen species (ROS) in both OSCC lines. To verify that the SIRT3 sequence variation was associated with oral carcinogenesis, we sequenced the SIRT3 gene from 21 OSCC patients, and 5 of the 21 patients (23.8%) carried the heterozygous missense mutation, p.Val208Ile. The heterozygous missense mutation in these patients was present in gremlin DNA isolated from both normal and tumor tissues.Conclusions: Our findings provide a valuable insight into the potential role of SIRT3 in the development of oral squamous cell carcinoma, by showing that a non-synonymous point mutation in SIRT3 contributes to reduced catalytic activity of the protein and affects redox balance in OSCCs.
原文英語
文章編號68
期刊Molecular Cancer
12
發行號1
DOIs
出版狀態已發佈 - 六月 23 2013
對外發佈Yes

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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    Chen, I. C., Chiang, W. F., Liu, S. Y., Chen, P. F., & Chiang, H. C. (2013). Role of SIRT3 in the regulation of redox balance during oral carcinogenesis. Molecular Cancer, 12(1), [68]. https://doi.org/10.1186/1476-4598-12-68