A cellular biological study on assessment of the deacetylase SIRT1 expression in oral squamous cell carcinoma

• Project/Area Number: 25861990
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: Noguchi Akira 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, その他 (10456395)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 頭頚部癌 / 口腔癌 / 扁平上皮癌 / ヒストン脱アセチル化酵素 / HDAC / SIRT1 / 頭頸部癌 / エピジェネティクス

Outline of Final Research Achievements

SIRT1 expression was assessed by immunohistochemistry conducted using samples from 437 consecutive HNSCC patients. IHC revealed 79.6% staining of SIRT1 in HNSCC. Multivariate analyses revealed that expression of SIRT1 was an independent and good indicator of prognosis. In contrast with HNSCC, high expression of SIRT1 was associated with progression and prognosis in 557 gastric cancer patients. Therefore, we examined whether SIRT1 promotes differentiation in HNSCC cells by evaluating the correlation between the expression of SIRT1 and several genes implicated in stemness or differentiation in HNSCC derived cell lines. RNA interference-mediated reduction of SIRT1 showed that SIRT1 supports the expression of TAp63, which has been implicated in tumor suppression, in addition to epithelial differentiation. It was possible that SIRT1 contributes to cancer progression by supporting the transcription of tumor-suppressive TAp63.

Research Products

• [Journal Article] Association of SIRT1 and the tumor-suppressor gene TAp63 expression in head and neck squamous cell carcinoma (2015)
  • Author(s): Kikuchi K, Noguchi A, Kasajima R, Miyagi Y, Hoshino D, Koshikawa N, Kubota A, Yokose T, Takano Y.
  • Journal Title: Tumor Biology Volume: in press Issue: 10 Pages: 7865-72
  • DOI: 10.1007/s13277-015-3515-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SIRT1 expression is associated with a poor prognosis, whereas DBC1 is associated with favorable outcomes in gastric cancer. (2014)
  • Author(s): Noguchi A, Kikuchi K, Zheng H, Takahashi H, Miyagi Y, Aoki I, Takano Y.
  • Journal Title: Cancer Med. Volume: 3 Issue: 6 Pages: 1553-61
  • DOI: 10.1002/cam4.310
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SIRT1 expression is associated with good prognosis for head and neck squamous cell carcinoma patients. (2013)
  • Author(s): Noguchi A, Li X, Kubota A, Kikuchi K, Kameda Y, Zheng H, Miyagi Y, Aoki I, Takano Y.
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Volume: 115 Issue: 3 Pages: 385-92
  • DOI: 10.1016/j.oooo.2012.12.013
  • Peer Reviewed