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Study on malignant transformation through DNA methylation in HPV16-positive oral squamous cell carcinoma

Research Project

Project/Area Number 18K09791
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHiroshima University

Principal Investigator

SUGIYAMA Masaru  広島大学, 医系科学研究科(歯), 名誉教授 (70187681)

Co-Investigator(Kenkyū-buntansha) 重石 英生  広島大学, 医系科学研究科(歯), 講師 (90397943)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHPV16 / 癌幹細胞 / 口腔癌 / 歯周病 / 歯周病原細菌 / 口腔扁平上皮癌 / HPV / CD44 / メチル化
Outline of Final Research Achievements

①In HPV16 E6/E7-positive oral squamous cell carcinoma cell line (UM-SCC-104), E6/E7 siRNA knockdown significantly reduced sphere colony formation ability and mRNA expression of stem cell markers (Oct4, Nanog, ALDH1). ② Methylation of CD44 gene was detected more frequently in HPV16-positive oral cancer than in HPV16-negative oral cancer. ③ Characteristic oral bacterial flora was found in the subjects with HPV16 DNA. Additionally, there was a significant relationship between the presence of HPV16 DNA and bleeding during periodontal probing.

Academic Significance and Societal Importance of the Research Achievements

①HPV16陽性口腔扁平上皮癌細胞の幹細胞性の維持には、E6/E7遺伝子が重要な役割を持つことが示唆された。また、HPV DNAが宿主ゲノムに結合している子宮頸癌細胞とは異なり、UM-SCC-104細胞中ではHPV16 DNAがエピゾームとして存在しているにも関わらず、E6/E7 siRNA ノックダウンにより幹細胞性が低下した。このことは、存在様式に関わらず、HPV DNAが細胞の悪性化に関与していることを示唆している。②HPV16 DNA がCD44のメチル化に関与している可能性が示唆された。③歯周病とHPV感染との関係が示唆された。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Detection of HPV16 E6 DNA in periodontal pockets of middle-aged and older people.2021

    • Author(s)
      Shigeishi H, Murodumi H, Ohta K, Sugiyama M.
    • Journal Title

      Oral Science International.

      Volume: 18 Pages: 50-55

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of oral HPV16 infection with periodontal inflammation and the oral microbiome in older Japanese women.2021

    • Author(s)
      Shigeishi H, Su CY, Kaneyasu Y, Matsumura M, Nakamura M, Ishikawa M, Saito A, Ohta K, Sugiyama M.
    • Journal Title

      Exp Ther Med.

      Volume: 21 Issue: 2 Pages: 167-167

    • DOI

      10.3892/etm.2020.9598

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review).2021

    • Author(s)
      Shigeishi H, Ohta K, Sugiyama M.
    • Journal Title

      Biomedical Reports

      Volume: 14 Pages: 40-40

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of HPV16 E6 DNA in periodontal pockets of middle-aged and older people.2021

    • Author(s)
      Shigeishi H, Murodumi H, Ohta K, Sugiyama M.
    • Journal Title

      Oral Sci Int

      Volume: 18 Issue: 1 Pages: 50-55

    • DOI

      10.1002/osi2.1079

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease.2021

    • Author(s)
      Shigeishi H, Sugiyama M, Ohta K.
    • Journal Title

      Biomed Rep

      Volume: 14 Pages: 40-40

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of oral bacteria on the tongue dorsum using PCR amplification of 16S ribosomal RNA and its association with systemic disease in middle-aged and elderly patients.2019

    • Author(s)
      Su CY, Shigeishi H, Nishimura R, Ohta K, Sugiyama M.
    • Journal Title

      Biomed Rep,

      Volume: 10 Pages: 70-76

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of hydrogel stiffness on morphology and gene expression pattern of CD44high oral squamous cell carcinoma cells.2019

    • Author(s)
      Shigeishi H, Yokoyama S, Murodumi H, Sakuma M, Kato H, Higashikawa K, Takechi M, Ohta K, Sugiyama M.
    • Journal Title

      Int J Clin Exp Pathol.

      Volume: 12 Pages: 2826-2836

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High HPV16 E6 viral load in the oral cavity is associated with an increased number of bacteria: A preliminary study.2018

    • Author(s)
      Shigeishi H, Sugiyama M, Ohta K, Yokoyama S, Sakuma M, Murozumi H, Kato H, Takechi M.
    • Journal Title

      Biomed Rep

      Volume: 8 Pages: 59-64

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human papillomavirus type 16 (HPV16) DNA copy number in oral rinse samples from oral cavity cancer patients.2018

    • Author(s)
      Shigeishi H, Yokoyama S, Ohta K, Takechi M, Sugiyama M.
    • Journal Title

      Translational Research in Oral Oncology

      Volume: 3 Pages: 1-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] HPV16 DNAと歯周病原細菌との関係.2021

    • Author(s)
      重石 英生,中村 真梨子,兼保 佳乃,杉山 勝,太田 耕司.
    • Organizer
      第70回日本口腔衛生学会・総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔のHPV16感染と歯周病原細菌との関係2020

    • Author(s)
      重石 英生, 中村 真梨子,杉山 勝,太田 耕司
    • Organizer
      第104回広島大学歯学会例会
    • Related Report
      2020 Research-status Report
  • [Presentation] Association between oral HPV prevalence and smoking in people without oral cancer2019

    • Author(s)
      Hideo Shigeishi, Masaru Sugiyama, Kouji Ohta
    • Organizer
      15th Annual Conference of the International Society for the Prevention of Tobacco Induced Diseases
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 口腔のHPV16と口腔衛生状態および歯周病原細菌との関係2019

    • Author(s)
      重石 英生,杉山 勝,太田 耕司
    • Organizer
      第28回日本口腔感染症学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] The association between oral HPV16 infection and oral health status in Japanese female aged 60 years and over2019

    • Author(s)
      Hideo Shigeishi, Cheng-Yih Su, Yoshino Kaneyasu, Mari Matsumura, Mariko Nakamura, Momoko Ishikawa, Ayumi Saito, Kouji Ohta, Masaru Sugiyama
    • Organizer
      第52回広島大学歯学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔HPV感染の危険因子およびHPV陽性口腔癌の分子生物学的特徴2018

    • Author(s)
      重石 英生, 太田 耕司,杉山 勝.
    • Organizer
      第67回日本口腔衛生学会・総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 口腔含嗽サンプルを用いたHuman Papillomavirus (HPV) DNAの陽性率の検討.2018

    • Author(s)
      重石 英生、太田 耕司,東川 晃一郎,武知 正晃,杉山 勝.
    • Organizer
      第47回(公社)日本口腔外科学会中国四国支部学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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