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molecular diagnosis and target therapy for cervical cancer by microRNA

Research Project

Project/Area Number 17K11300
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionFujita Health University

Principal Investigator

FUJII TAKUMA  藤田医科大学, 医学部, 教授 (10218969)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords子宮頸がん / マイクロRNA / 子宮頸部異形成 / 検診 / 分子標的治療 / 分子診断 / 細胞増殖 / マイクロアレイ / microRNA / 診断 / 遺伝子 / 医療 / 転写制御 / がん
Outline of Final Research Achievements

MicroRNAs (miRNAs) play important roles in the regulation of gene expression during cervical carcinogenesis. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) in cervical mucus were significantly upregulated in precancer and cancer compared with normal, and their expression levels correlated with the disease severity. miRNAs in cervical mucus are promising biomarkers for cervical cancer and its precursor lesions.
Next, we investigated the effects of enforced miR-126-3p expression in the cervical cancer cell line, HeLa. In miR-126-3p-transfected cells, p85b, p110a, p-PDK1, p- AKT, p-GSK3b, CyclinD1, MRCKa, ROCK1, and p- PLCg1 were downregulated, Bad and Bax were upregulated, whereas Bcl-xL expression was downregulated, resulting in increased caspase3/7 activity and apoptosis. High levels of miR-126-3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR-126-3p could represent a new approach for treating patients with cervical cancer.

Academic Significance and Societal Importance of the Research Achievements

子宮頸がんスクリーニング法は細胞診で行われているが、欧米諸国の臨床試験の結果では感度7割と高くない。頸管粘液中のmiRNAには頸部前がん病変から過剰発現しているものがあり、それを計測することで早期補助診断が可能であることが分かった。このmiRNAは細胞内に強制的に発現すると癌細胞の増殖を抑制することがわかり、新たな子宮頸がんに対する分子標的治療開発の可能性も示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (34 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 6 results) Presentation (17 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] MicroRNA-126-3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway2020

    • Author(s)
      Fujii Takuma、Ichikawa Ryoko、Kawasaki Rie、Iwata Aya、Otani Sayaka、Nishio Eiji、Nomura Hiroyuki
    • Journal Title

      Oncology Reports

      Volume: 43 Pages: 1300-1308

    • DOI

      10.3892/or.2020.7512

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinically Needed Knowledge of the Human Papillomavirus Genotype2019

    • Author(s)
      Fujii T
    • Journal Title

      Nihon Kikan Shokudoka Gakkai Kaiho

      Volume: 70 Issue: 2 Pages: 75-76

    • DOI

      10.2468/jbes.70.75

    • NAID

      130007636927

    • ISSN
      0029-0645, 1880-6848
    • Year and Date
      2019-04-10
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions2019

    • Author(s)
      Otani S, Fujii T, Kukimoto I, Yamamoto N, Tsukamoto T, Ichikawa R, Nishio E, Iwata A.
    • Journal Title

      Cytokine

      Volume: 120 Pages: 210-219

    • DOI

      10.1016/j.cyto.2019.05.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of primary signet-ring cell carcinoma of the cervix containing full genome of human papillomavirus 162019

    • Author(s)
      Kawai S, Torii Y, Kukimoto I, Fujii T.
    • Journal Title

      Indian J Pathol Microbiol.

      Volume: 62 Issue: 1 Pages: 146-148

    • DOI

      10.4103/ijpm.ijpm_507_17

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] コルポスコープで観察できる子宮頸部・腟内病変2019

    • Author(s)
      藤井多久磨
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 71 Pages: 1580-1585

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 臨床に必要なヒトパピローマウイルス型とゲノムの基礎知識2019

    • Author(s)
      藤井多久磨
    • Journal Title

      日本気管食道科学会会報, 70(2):75-76

      Volume: 70 Pages: 75-76

    • NAID

      130007636927

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia2018

    • Author(s)
      Fujii Takuma、Kawai Satoshi、Kukimoto Iwao、Yamada Hiroya、Yamamoto Naoki、Kuroda Makoto、Otani Sayaka、Ichikawa Ryoko、Nishio Eiji、Torii Yutaka、Iwata Aya
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-018-25310-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Twin pregnancy with chromosomal abnormalities mimicking a gestational trophoblastic disorder and coexistent foetus on ultrasound2018

    • Author(s)
      Ohwaki Akiko、Nishizawa Haruki、Aida Noriko、Kato Takema、Kambayashi Asuka、Miyazaki Jun、Ito Mayuko、Urano Makoto、Kiriyama Yuka、Kuroda Makoto、Nakayama Masahiro、Sonta Shin-Ichi、Suzumori Kaoru、Sekiya Takao、Kurahashi Hiroki、Fujii Takuma
    • Journal Title

      Journal of Obstetrics and Gynaecology

      Volume: - Issue: 7 Pages: 1-3

    • DOI

      10.1080/01443615.2017.1401598

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiplex PCR in noninvasive prenatal diagnosis for FGFR3-related disorders2018

    • Author(s)
      Terasawa Sumire、Kato Asuka、Nishizawa Haruki、Kato Takema、Yoshizawa Hikari、Noda Yoshiteru、Miyazaki Jun、Ito Mayuko、Sekiya Takao、Fujii Takuma、Kurahashi Hiroki
    • Journal Title

      Congenital Anomalies

      Volume: - Issue: 1 Pages: 1-7

    • DOI

      10.1111/cga.12278

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful fertility-sparing surgery and chemotherapy for stage Ⅰc3 ovarian cancer with the postoperative use of the traditional Japanese herbal formulation hachimijiogan2017

    • Author(s)
      Nishio E, Kawai S, Akita E, Fujii T
    • Journal Title

      Traditonal & Kampo medicine

      Volume: 4 Pages: 124-126

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] コルポスコピー検査(解説)2017

    • Author(s)
      藤井多久磨
    • Journal Title

      東海産科婦人科学会雑誌

      Volume: 53 Pages: 43-47

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 当院における腹腔鏡下子宮体癌手術の術前診断の精度2017

    • Author(s)
      河合智之、鳥居 裕、大谷清香、市川亮子、植田高弘、藤井多久磨
    • Journal Title

      日本婦人科腫瘍学会雑誌

      Volume: 35 Pages: 1-7

    • NAID

      40021099808

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 当院での子宮頸部円錐切除術術後出血に関する検討2017

    • Author(s)
      寺澤すみれ、鳥居 裕、宮崎 純、大脇晶子、小川千紗、坂部慶子、野田佳照、大谷清香、伊藤真友子、市川亮子、宮村浩徳、西澤春紀、西尾永司、藤井多久磨
    • Journal Title

      東海産科婦人科学会雑誌

      Volume: 53 Pages: 293-297

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 高度ダグラス窩癒着症例に対する子宮全摘術-Three-step total laparoscopic hysterectomy-の手術成績2017

    • Author(s)
      野田佳照、廣田 穣、秋田絵理、大脇晶子、宮﨑 純、河合智之、坂部慶子、伊藤真友子、大谷清香、藤井多久磨、小川千紗、酒向隆博
    • Journal Title

      東海産婦人科内視鏡手術研究会雑誌

      Volume: 5 Pages: 53-60

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Association between community state of vaginal microbiota and cervical cytokine profile in patients with CIN2020

    • Author(s)
      Fujii T, Kawahara R, Kukimoto I, Ichikawa R, Miki M, Kanao S, Nomura H, Torii Y, Iwata A
    • Organizer
      ASCCP 2020 Annual Scientific Meeting on Anogenital and HPV-Related Diseases
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lecture - Current status and future task for cervical cancer screening in Japan2019

    • Author(s)
      Fujii T
    • Organizer
      JHU-ASC-JSCC Joint Cytopathology Course 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Gynae Symposium I- Current Status of Cervical Cancer Prevention UK, New Zealand, USA and Japan: Crossroads for Primary and Secondary Cervical Cancer Prevention in Japan2019

    • Author(s)
      Fujii T
    • Organizer
      20th International Congress of Cytology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 教育講演 コルポスコープ検査2019

    • Author(s)
      藤井多久磨
    • Organizer
      第60回日本臨床細胞学会総会(春期大会)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 教育講演 コルポスコープで観察できる子宮頸部・腟内病変2019

    • Author(s)
      藤井多久磨
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 頸管粘液中のmicro RNAは子宮頸がんおよびその前癌病変診断のバイオマーカーとして有用である2019

    • Author(s)
      大谷清香、市川亮子、鳥居 裕、西尾永司、藤井多久磨
    • Organizer
      第7回婦人科がんバイオマーカー研究会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 高齢者においてHSILと判定された患者の組織診断の特徴2019

    • Author(s)
      大谷清香、市川亮子、塚本徹哉、平澤 浩、藤井多久磨
    • Organizer
      第38回日本臨床細胞学会東海連合会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cytokine profile of the cervical mucus in patients with cervical cancer and its precursor lesions2018

    • Author(s)
      Otani S, Fujii T, Kukimoto I, Iwata A, Ichikawa R, Tsukamoto T.
    • Organizer
      The 17th Biennial Meeting of the International Gynecologic Cancer Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] MicroRNAs in the cervical mucus are promising biomarkers for cervical cancer and cervical neoplasia2018

    • Author(s)
      Kawai S,Otani S,Ichikawa R,Torii Y,Nishio E,Fujii T
    • Organizer
      第70回日本産科婦人科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 臨床に必要なヒトパピローマウイルス型とゲノムの基礎知識2018

    • Author(s)
      藤井多久磨
    • Organizer
      第70回日本気管食道科学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] mir-126-3pは子宮頸部の発がん過程においてPI3K/AKT経路を制御している2018

    • Author(s)
      藤井多久磨
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ロボット支援下手術の普及に必要なこと2018

    • Author(s)
      藤井多久磨
    • Organizer
      第6回日本婦人科ロボット手術研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Surgical anatomy of gynecologic malignancies by cadaveric study2017

    • Author(s)
      Kawai S, Imanishi N, Fujii T
    • Organizer
      The 5th Biennial Meeting of Asian Society of Gynecologic Oncology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 専攻医教育プログラム 1-2 コルポスコピー検査2017

    • Author(s)
      藤井多久磨
    • Organizer
      第137回東海産科婦人科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] HPVワクチンを取り巻く環境 HPVワクチンの世界での現状と課題2017

    • Author(s)
      藤井多久磨
    • Organizer
      第59回日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] マイクロRNAによる子宮頸癌スクリーニング法の開発2017

    • Author(s)
      藤井多久磨、柊元厳
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 婦人科悪性腫瘍手術においては手術解剖に熟知することが重要である2017

    • Author(s)
      藤井多久磨
    • Organizer
      第30回日本内視鏡外科学会総会
    • Related Report
      2017 Research-status Report
  • [Book] 産科婦人科疾患最新の治療2019-20212019

    • Author(s)
      鳥居 裕、藤井多久磨(吉川 史隆、平松 祐司、大須賀 穣編)
    • Total Pages
      314
    • Publisher
      南江堂
    • ISBN
      9784524246427
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 子宮頸がん検査用検体2018

    • Inventor(s)
      藤井多久磨
    • Industrial Property Rights Holder
      藤井多久磨
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-118960
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 子宮頸がん検査用検体2017

    • Inventor(s)
      藤井多久磨
    • Industrial Property Rights Holder
      藤井多久磨
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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