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

Molecular Cancer

Research

Shyun-Yeu Liu¹  Wei-Fan Chiang²  I-Chieh Chen³  Pei-Fen Chen³  Hung-Che Chiang⁴ 

[1] Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;School of Dentistry, Yang-Ming University, Taipei, Taiwan;Division of Environmental Health and Occupational Medicine, National Health, Research Institutes, No. 35, Keyan Road, 35053, Zhunan, Miaoli, Taiwan;Division of Environmental Health and Occupational Medicine, National Health, Research Institutes, No. 35, Keyan Road, 35053, Zhunan, Miaoli, Taiwan;National Environmental Health Research Center, National Health Research Institutes, Miaoli, Taiwan;Department of Occupational Medicine, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan;

关键词: Sirtuin 3;    Reactive oxygen species;    Oral squamous cell carcinoma;    Human oral keratinocyte;   

DOI  :  10.1186/1476-4598-12-68

 received in 2013-01-09, accepted in 2013-05-10,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundSirtuins (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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Chen et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.