Explore the role of poly ADP ribose polymerase on chemo-sensitivity in HPV-related oral cancer

• Project/Area Number: 18K17030
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Uehara Karina 琉球大学, 医学部, 助教 (30782594)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HPV / PARP / 口腔がん / 治療感受性 / 口腔癌 / ポリADPリボースポリメラーゼ

Outline of Final Research Achievements

Human papillomavirus (HPV) related oral cancer shows high chemo-sensitivity with better prognosis, but its mechanism remains uncertain. Mouse embryonic fibroblasts expressing HPV16 E6 upregulate poly ADP ribose polymerase (PARP) and induce poly ADP ribosylation. We hypothesized that PARP and poly ADP ribosylation is related with chemo-sensitivity in HPV-related oral cancer. We found high-risk HPV infection such as HPV16 or HPV18 increases PARP in oral cancer formalin-fixed paraffin-embedded samples, but the association between HPV infection and PARP, that between PARP and chemo-sensitivity was not observed in vitro. In this study, we suggest HPV infection may induce high PARP expression in oral cancer. Further analysis is needed to confirm what factor influences better prognosis in HPV-related oral cancer.

Academic Significance and Societal Importance of the Research Achievements

ヒトパピローマウイルス (HPV) 陽性口腔がんは、DNA修復酵素として知られるポリADPリボースポリメラーゼ (PARP) 発現を誘導することが明らかとなり、HPV感染とPARP発現の関連が示唆された。今回、PARP発現と治療感受性の直接的な関連を明らかにすることはできなかったが、PARP活性が口腔がんのHPV陽性マーカーとして臨床応用に発展できる可能性がある。また、病理組織標本を用いてHPV感染とPARP発現を比較する際に、HPV型の特定を行った。引き続き、口腔がんとHPV感染の解析を進めることで、口腔がんにおける予後不良のHPV型を特定することができ、臨床上有益なデータを提供できる。

Research Products

• [Journal Article] K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation (2019)
  • Author(s): Tamanaha-Nakasone Ayumi、Uehara Karina、Tanabe Yasuka、Ishikawa Haruna、Yamakawa Natsuko、Toyoda Zensei、Kurima Kiyoto、Kina Shinichiro、Tsuneki Masayuki、Okubo Yuko、Yamaguchi Sayaka、Utsumi Daisuke、Takahashi Kenzo、Arakawa Hirofumi、Arasaki Akira、Kinjo Takao
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-019-42763-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] AIDS関連型カポジ肉腫と古典型カポジ肉腫由来KSHV K1遺伝子の形質転換能と臨床像の関連 (2019)
  • Author(s): 上原佳里奈、喜名振一郎、新崎章、金城貴夫
  • Organizer: 日本病理学会
• [Presentation] 口腔がんにおけるlow-risk HPV E6とEBV LMP-1の二重発現細胞を用いた形質転換能の比較 (2019)
  • Author(s): 上原佳里奈、喜名振一郎、新崎章、金城貴夫
  • Organizer: 日本病理学会