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Analysis of cancer pathogenesis regulated by tissue-specific non-coding RNA

Research Project

Project/Area Number 16K11496
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionFukuoka University

Principal Investigator

Kawakubo-Yasukochi Tomoyo  福岡大学, 薬学部, 講師 (70507813)

Research Collaborator Morioka Masahiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords口腔癌 / エクソソーム / miRNA / がん / 浸潤 / non-coding RNA / 口腔扁平上皮癌 / 乳癌
Outline of Final Research Achievements

In this project, we demonstrated the spread of the invasive or metastatic potential between oral squamous carcinoma cell clones, SQUU-A (nonmetastatic) and SQUU-B (highly-metastatic) established from local recurrence events of a tongue cancer, derived from the same tumor mass was mediated by exosomes. We further challenged miRNA-mRNA pairing analysis by the use of exosomes originated by those cell clones, and identified the possible miRNA (miR-200c-3p) and its downstream mRNAs (WRN and CHD9) responsible for invasive potential.
Our findings offer insights that each malignant cell clone in an identical tumor mass secreted each unique exosome that encapsulates specific miRNAs, and that miRNAs could undertake crosstalk among different malignant cell clones in an identical tumor microenvironment to regulate clinical prognosis.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、腫瘍組織内の多様ながん細胞が分泌するエクソソームには、それぞれ固有の発現パターンを示すmiRNAが内包されていること、さらにエクソソームによって運ばれたmiRNAは、標的細胞内で遺伝子発現を制御することでがんの微小環境を規定していることが示唆された。
生体内におけるmiRNAは細胞外でもRNA結合蛋白質複合体やエクソソームなどの膜小胞に包まれて安定な状態で体液中に存在することから、安定性が高く非侵襲的バイオマーカーとして期待されている。よって、今回同定したmiRNAや標的遺伝子の異常をがんの予後予測因子として提示することが可能である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (45 results)

All 2019 2018 2017 2016

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 9 results,  Acknowledgement Compliant: 6 results) Presentation (30 results) (of which Int'l Joint Research: 12 results,  Invited: 2 results)

  • [Journal Article] Maternal Folic Acid Depletion during Early Pregnancy Increases Sensitivity to Squamous Tumor Formation in the Offspring in Mice2019

    • Author(s)
      Kawakubo-Yasukochi T, Morioka M, Ohe K, Yasukochi A, Ozaki Y, Hazekawa M, Nishinakagawa T, Ono K, Nakamura S, Nakashima M.
    • Journal Title

      J Dev Orig Health Dis

      Volume: in press

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of collagen type XVII expression by miR203a-3p in oral squamous cell carcinoma cells2019

    • Author(s)
      Yasukochi A, Kawakubo-Yasukochi T, Morioka M, Hazekawa M, Nishinakagawa T, Ono K, Nakashima M, Nakamura S.
    • Journal Title

      J Biochem

      Volume: in press Issue: 2 Pages: 163-173

    • DOI

      10.1093/jb/mvz024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>In Vitro</i> Anti-inflammatory Effects of the Phenylbutyric Acid Metabolite Phenylacetyl Glutamine2018

    • Author(s)
      Hazekawa M, Ono K, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 6 Pages: 961-966

    • DOI

      10.1248/bpb.b17-00799

    • NAID

      130007382724

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-06-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment.2018

    • Author(s)
      Kawakubo-Yasukochi T, Morioka M, Hazekawa M, Yasukochi A, Nishinakagawa T, Ono K, Kawano S, Nakamura S, Nakashima M.
    • Journal Title

      Mol Carcinog

      Volume: 57 Issue: 2 Pages: 295-302

    • DOI

      10.1002/mc.22744

    • NAID

      120006900039

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth.2017

    • Author(s)
      Hayashi Y, Kawakubo-Yasukochi T, Mizokami A, Hazekawa M, Yakura T, Naito M, Takeuchi H, Nakamura S, Hirata M.
    • Journal Title

      J Cancer

      Volume: 8 Issue: 13 Pages: 2478-2486

    • DOI

      10.7150/jca.18648

    • NAID

      120006900041

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-inflammatory effects of water extract from bell pepper (Capsicum Annuum L. var. grossum) leaves in vitro.2017

    • Author(s)
      Hazekawa M, Hideshima Y, Ono K, Nishinakagawa T, Kawakubo-Yasukochi T, Takatani-Nakase T, Nakashima M.
    • Journal Title

      Ex Ther Med

      Volume: 14 Pages: 4349-4355

    • DOI

      10.3892/etm.2017.5106

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of cytotoxicity of imatinib for oral squamous cell carcinoma by real-time analysis system.2017

    • Author(s)
      Hazekawa M, Morioka M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakamura S, Nakashima M.
    • Journal Title

      eJBio

      Volume: 13 Pages: 56-62

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential roles of carboxylated and uncarboxylated osteocalcin in prostate cancer growth2016

    • Author(s)
      Hayashi, Y., Kawakubo-Yasukochi, T., Mizokami, A., Takeuchi, H., Nakamura, S. and Hirata, M.
    • Journal Title

      J. Cancer

      Volume: 7 Issue: 12 Pages: 1605-1609

    • DOI

      10.7150/jca.15523

    • NAID

      120006900040

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Uncarboxylated osteocalcin increases serum nitric oxide levels and ameliorates hypercholesterolemia in mice fed an atherogenic diet.2016

    • Author(s)
      Kondo A, Kawakubo-Yasukochi T (corresponding author), Mizokami A, Chishaki S, Takeuchi H, Hirata M.
    • Journal Title

      eJBio

      Volume: 13 Pages: 22-28

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effect of collagen type I or human fibronectin on imatinib cytotoxicity in oral squamous cell carcinoma.2016

    • Author(s)
      Morioka M, Hazekawa M, Kawakubo-Yasukochi T, Nishinakagawa T, Nakamura S, Nakashima M.
    • Journal Title

      Pharmacology & Pharmacy

      Volume: 7 Issue: 07 Pages: 255-263

    • DOI

      10.4236/pp.2016.77032

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes from oral squamous carcinoma cell lines, SQUU-A and SQUU-B, define the tropism of lymphatic dissemination.2016

    • Author(s)
      Morioka M, Kawakubo-Yasukochi T (corresponding author), Hayashi Y, Hazekawa M, Nishinakagawa T, Ono K, Kawano S, Nakamura S, Nakashima M.
    • Journal Title

      J Oral Biosci

      Volume: 58 Issue: 4 Pages: 180-184

    • DOI

      10.1016/j.job.2016.05.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Maternal oral administration of osteocalcin protects offspring from metabolic impairment in adulthood2016

    • Author(s)
      *Kawakubo-Yasukochi T, Kondo A, Mizokami A, Hayashi Y, Chishaki S, Nakamura S, Takeuchi H, Hirata M.
    • Journal Title

      Obesity

      Volume: 24 Issue: 4 Pages: 895-907

    • DOI

      10.1002/oby.21447

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet2016

    • Author(s)
      Yasutake Y., Mizokami A., Kawakubo-Yasukochi T., Chishaki S., Takahashi I., Takeuchi H., Hirata M.
    • Journal Title

      Am. J. Physiol. Endocrinol. Metab.

      Volume: 310 Issue: 8 Pages: E662-E675

    • DOI

      10.1152/ajpendo.00334.2015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The SQUU-B cell line spreads its metastatic properties to nonmetastatic clone SQUU-A from the same patient through exosomes.2016

    • Author(s)
      Kawakubo-Yasukochi T (corresponding author), Morioka M, Hayashi Y, Nishinakagawa T, Hazekawa M, Kawano S, Nakamura S, Nakashima M.
    • Journal Title

      J Oral Biosci

      Volume: 58 Issue: 1 Pages: 33-38

    • DOI

      10.1016/j.job.2015.10.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hazekawa M, Morioka M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakamura S, Nakashima M.2016

    • Author(s)
      Assessment of cytotoxicity of imatinib for oral squamous cell carcinoma by a real-time cell analysis system
    • Journal Title

      eJBio

      Volume: 13 Pages: 56-62

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment2019

    • Author(s)
      Kawakubo-Yasukochi T, Morioka M, Hazekawa M, Nishinakagawa T, Yasukochi A, Nakamura S, Nakashima M.
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 妊娠母体が飲用する胎盤通過性オステオカルシンが胎児の糖脂質代謝関連臓器のエピジェネティックな変化に及ぼす影響2018

    • Author(s)
      安河内(川久保)友世
    • Organizer
      DIJFカンファレンス
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 抗炎症作用を有するピーマン葉水抽出エキス中の成分探索2018

    • Author(s)
      櫨川舞、小野和彦、西中川拓也、安河内(川久保)友世、中島学
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] PBA投与後血清中に誘導される抗炎症活性本体の解明2018

    • Author(s)
      小野和彦、櫨川舞、西中川拓也、安河内(川久保)友世、中島学
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] PBA投与による血中マウスDSS誘発性IBD発症抑制性物質の探索2017

    • Author(s)
      小野和彦、櫨川舞、西中川拓也、安河内(川久保)友世、中島学
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] PBA代謝物PAGlnの抗炎症作用に関するin vitro評価2017

    • Author(s)
      櫨川舞、小野和彦、西中川拓也、安河内友世、中島学
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] The significance of BP180 expression in oral squamous carcinoma cell invasion2017

    • Author(s)
      Yasukochi A, Morioka M, Kawakubo-Yasukochi T, Nakashima M, Nakamura S.
    • Organizer
      The 5th ASHNO Congress 2017, Congress of Asian Society of Head and Neck Oncology
    • Place of Presentation
      Bali, Indonesia
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exosome-mediated crosstalk determines invasiveness and organotropic metastasis in oral squamous cell carcinoma2017

    • Author(s)
      Morioka M, Kawakubo-Yasukochi T, Hazekawa M, Nishinakagawa T, Ono K, Kawano S, Nakamura S, Nakashima M.
    • Organizer
      The 5th ASHNO Congress 2017, Congress of Asian Society of Head and Neck Oncology
    • Place of Presentation
      Bali, Indonesia
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 卵巣がんにおけるsiRNA-PLGAハイブリッドミセル製剤の遺伝子抑制による治療効果2017

    • Author(s)
      櫨川舞、西中川拓也、安河内友世、中島学
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Exosomes from oral squamous carcinoma cells define the tropism of invasiveness and lymphatic dissemination2017

    • Author(s)
      Morioka M, Kawakubo-Yasukochi T, Nakamura S, Nakashima M.
    • Organizer
      Kyudai Oral Bioscience
    • Place of Presentation
      Fukuoka, JAPAN
    • Year and Date
      2017-02-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Uncarboxylated osteocalcin prevents cancer progression through multiple mechanisms including immune system2017

    • Author(s)
      Hayashi Y, Kawakubo-Yasukochi T, Mizokami A, Nakamura S, Hirata M.
    • Organizer
      Kyudai Oral Bioscience
    • Place of Presentation
      Fukuoka, JAPAN
    • Year and Date
      2017-02-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 口腔扁平上皮癌細胞由来エクソソームによるがん微小環境制御とリンパ行性転移の規定2017

    • Author(s)
      森岡政彦、安河内(川久保)友世、中村誠司
    • Organizer
      第71回日本口腔科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Preparation of self-assembled siRNA-PLGA hybrid conjugate micelles as GPC-3 gene silencing therapy for ovarian cancer2017

    • Author(s)
      Hazekawa M, Morioka M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakamura S, Nakashima M
    • Organizer
      The 6th Pharmaceutical Sciences World Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 妊娠母体が摂取したオステオカルシンが次世代に及ぼす影響2017

    • Author(s)
      川久保-安河内友世、近藤皓彦、溝上顕子、平田雅人
    • Organizer
      第6回日本DOHaD学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Therapeutic effects of self-assembled siRNA-PLGA hybrid conjugate micelles for ovarian cancer2017

    • Author(s)
      Hazekawa M, Morioka M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakamura S, Nakashima M.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 非コードRNAによる口腔癌の進展制御2017

    • Author(s)
      川久保-安河内友世、森岡政彦、安河内篤、中村誠司、中島学
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔扁平上皮癌におけるBP180の局在2017

    • Author(s)
      安河内篤、森岡政彦、川久保-安河内友世、中島学、中村誠司
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔扁平上皮癌におけるAT1受容体拮抗薬の影響2017

    • Author(s)
      森岡政彦、川久保-安河内友世、中村誠司、中島学
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Microenvironmental communications within oral squamous cell carcinoma defined by exosomes2017

    • Author(s)
      Morioka M, Kawakubo-Yasukochi T, Hazekawa M, Nishinakagawa T, Ono K, Kawano S, Nakamura S, Nakashima M.
    • Organizer
      第65回国際歯科研究学会日本部会総会・学術大会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Link of BP180 bullous pemphigoid autoantigen to invasion of oral squamous carcinoma cell2016

    • Author(s)
      Yasukochi A, Morioka M, Kawakubo-Yasukochi T, Obayashi K, Nakashima M, Nakamura S.
    • Organizer
      Australian and New Zealand Head & neck cancer society
    • Place of Presentation
      Auckland, New Zealand
    • Year and Date
      2016-10-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Intercelluler crosstalk defined by exosomes from oral squamous carcinoma cells determines its pathological process2016

    • Author(s)
      Morioka M, Kawakubo-Yasukochi T, Hazekawa M, Nishinakagawa T, Ono K, Kawano S, Nakamura S, Nakashima M.
    • Organizer
      Australian and New Zealand Head & neck cancer society
    • Place of Presentation
      Auckland, New Zealand
    • Year and Date
      2016-10-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Assessment of cytotoxicity of anticancer reagents for oral squamous cell carcinomas using a real-time cell monitoring analysis system2016

    • Author(s)
      Hazekawa M, Morioka M, Nishinakagawa T, Yasukochi T, Nakashima M.
    • Organizer
      Australian and New Zealand Head & neck cancer society
    • Place of Presentation
      Auckland, New Zealand
    • Year and Date
      2016-10-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] オステオカルシンを用いた次世代生活習慣病改善へのアプローチ2016

    • Author(s)
      安河内(川久保)友世、近藤皓彦、溝上顕子、竹内弘、平田雅人
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Application of real-time cell monitoring device in evaluation the IC50 levels of anticancer reagents2016

    • Author(s)
      Hazekawa M, Morioka M, Nishinakagawa T, Yasukochi T, Nakashima M.
    • Organizer
      第75回日本癌学会学術大会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Identify of the cytotoxic factor secreted by tumor cell line2016

    • Author(s)
      Nishinakagawa T, Hazekawa M, Yasukochi T, Nakashima M.
    • Organizer
      第75回日本癌学会学術大会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 癌の増殖における非(低)カルボキシル化オステオカルシンの機能2016

    • Author(s)
      林慶和、川久保-安河内友世、溝上顕子、中村誠司、竹内弘、平田雅人
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔扁平上皮癌細胞由来エクソソームによる細胞間クロストークと病態形成2016

    • Author(s)
      森岡政彦、川久保-安河内友世、中村 誠司
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] The effect of uncarboxylated osteocalcin on cancer growth2016

    • Author(s)
      Hayashi Y, Kawakubo-Yasukochi T, Mizokami A, Nakamura S, Takeuchi H, Hirata M.
    • Organizer
      The 9th Korea-Japan conference on cellular signaling for young scientists
    • Place of Presentation
      Seol, Korea
    • Year and Date
      2016-07-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of uncarboxylated osteocalcin in prevention of early atherosclerosis2016

    • Author(s)
      Kondo A, Kawakubo-Yasukochi T, Mizokami A, Takeuchi H, Hirata M.
    • Organizer
      The 9th Korea-Japan conference on cellular signaling for young scientists
    • Place of Presentation
      Seol, Korea
    • Year and Date
      2016-07-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] New functions of osteocalcin in cancer progression2016

    • Author(s)
      Hayashi Y, Kawakubo-Yasukochi T, Nakamura S, Hirata M.
    • Organizer
      The 57th Congress of the Korean Association of Oral Maxillofacial Surgeons
    • Place of Presentation
      Gunsan, Korea
    • Year and Date
      2016-04-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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