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B7H3 as a promising therapeutic target for endometrial cancer

Research Project

Project/Area Number 19K09769
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionHokkaido University

Principal Investigator

Ihira Kei  北海道大学, 医学研究院, 特任助教 (50813820)

Co-Investigator(Kenkyū-buntansha) 董 培新  北海道大学, 医学研究院, 特任助教 (50602504)
Project Period (FY) 2019-04-01 – 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 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsB7H3 / 子宮体癌 / B7H3 / 体癌 / Endometrial cancer
Outline of Research at the Start

新規免疫チェックポイント分子B7H3は、癌細胞に対する免疫細胞の攻撃力を弱め、癌細胞悪性形質の獲得にも寄与する。B7H3の過剰発現に関わるmiR-26a/148b/199及び長鎖非翻訳RNA (HOTAIR) は、子宮体癌(体癌)で発現変動し、その発現制御によりB7H3の発現を抑えることで、免疫抑制環境を解除し、体癌細胞の悪性形質を抑制することによって、体癌の進展を抑えることができる。

Outline of Final Research Achievements

The new immune checkpoint molecule B7H3 reduces the capacity of immune cells to target cancer cells and leads to cancer progression. Using our previously established highly invasive subline and cancer stem cell-like sphere cells and the CRISPR/Cas9 method, we attempted to elucidate the role of B7H3 in the acquisition of malignant features in endometrial cancer cells as well as the regulatory mechanism of B7H3 expression by CTDSPL, miR-199a, and mutant p53. Down-regulation of the CTDSPL gene and miR-199a, as well as mutant p53, all contribute to the acquisition of malignant features in endometrial cancer cells by increasing B7H3 expression and activating downstream PI3K/AKT and STAT3 pathways, implying that B7H3 is a novel therapeutic target for endometrial cancer. According to our results, B7H3 may be a potential therapeutic target for endometrial cancer.

Academic Significance and Societal Importance of the Research Achievements

体癌は最も頻度の高い婦人科悪性腫瘍の一つであり、患者数(特に若い世代)は年々増加傾向にある。体癌の進展に関わる分子基盤は十分には理解されておらず、依然として有望な創薬標的分子の同定は急務である。そこで、体癌において、癌の進展の促進に重要な役割を果たすB7H3を見出して、その関連分子経路を解明した。今後B7H3を標的することで、体癌細胞の転移能を阻害することができれば、体癌の新しい治療法を創出する可能性がある。

Report

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

    (27 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (6 results) Journal Article (13 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] University of Tennessee(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Sun Yat-sen University Cancer Center(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Tennessee(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] un Yat-sen University Cancer Center(中国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Tennessee(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Sun Yat-sen University Cancer Center(中国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] PIWI-Interacting RNAs (piRNAs): Promising Applications as Emerging Biomarkers for Digestive System Cancer2022

    • Author(s)
      Cai Aiting、Hu Yuhao、Zhou Zhou、Qi Qianyi、Wu Yixuan、Dong Peixin、Chen Lin、Wang Feng
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 9 Pages: 848105-848117

    • DOI

      10.3389/fmolb.2022.848105

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LncRNAs: Novel Biomarkers for Pancreatic Cancer2021

    • Author(s)
      Ghafouri-Fard Soudeh、Fathi Mohadeseh、Zhai Tianyue、Taheri Mohammad、Dong Peixin
    • Journal Title

      Biomolecules

      Volume: 11 Issue: 11 Pages: 1665-1665

    • DOI

      10.3390/biom11111665

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway2021

    • Author(s)
      Dong Peixin、Xiong Ying、Konno Yosuke、Ihira Kei、Kobayashi Noriko、Yue Junming、Watari Hidemichi
    • Journal Title

      Journal of Experimental Clinical Cancer Research

      Volume: 40 Issue: 1 Pages: 216-232

    • DOI

      10.1186/s13046-021-02018-1

    • NAID

      120007099136

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway2021

    • Author(s)
      Zhao Guannan、Zhang Wenjing、Dong Peixin、Watari Hidemichi、Guo Yuqi、Pfeffer Lawrence M.、Tigyi Gabor、Yue Junming
    • Journal Title

      Cell and Bioscience

      Volume: 11 Issue: 1 Pages: 70-82

    • DOI

      10.1186/s13578-021-00578-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications2021

    • Author(s)
      Dong Peixin、Xiong Ying、Konno Yosuke、Ihira Kei、Xu Daozhi、Kobayashi Noriko、Yue Junming、Watari Hidemichi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 425-436

    • DOI

      10.3389/fcell.2021.656993

    • NAID

      120006980025

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers2020

    • Author(s)
      Dong Peixin、Xu Daozhi、Xiong Ying、Yue Junming、Ihira Kei、Konno Yosuke、Watari Hidemichi
    • Journal Title

      Cancers

      Volume: 12 Issue: 6 Pages: 1472-1472

    • DOI

      10.3390/cancers12061472

    • NAID

      120006849869

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zinc regulates primary ovarian tumor growth and metastasis through the epithelial to mesenchymal transition2020

    • Author(s)
      Zhang Ruitao、Zhao Guannan、Shi Huirong、Zhao Xinxin、Wang Baojin、Dong Peixin、Watari Hidemichi、Pfeffer Lawrence M.、Yue Junming
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 160 Pages: 775-783

    • DOI

      10.1016/j.freeradbiomed.2020.09.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PD-L1 Is a Tumor Suppressor in Aggressive Endometrial Cancer Cells and Its Expression Is Regulated by miR-216a and lncRNA MEG32020

    • Author(s)
      Xu Daozhi、Dong Peixin、Xiong Ying、Chen Rui、Konno Yosuke、Ihira Kei、Yue Junming、Watari Hidemichi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 598205-598221

    • DOI

      10.3389/fcell.2020.598205

    • NAID

      120006940619

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MicroRNA-361-Mediated Inhibition of HSP90 Expression and EMT in Cervical Cancer Is Counteracted by Oncogenic lncRNA NEAT12020

    • Author(s)
      Xu Daozhi、Dong Peixin、Xiong Ying、Yue Junming、Konno Yosuke、Ihira Kei、Kobayashi Noriko、Todo Yukiharu、Watari Hidemichi
    • Journal Title

      Cells

      Volume: 9 Issue: 3 Pages: 632-632

    • DOI

      10.3390/cells9030632

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes2019

    • Author(s)
      Dong Peixin、Xiong Ying、Yue Junming、Xu Daozhi、Ihira Kei、Konno Yosuke、Kobayashi Noriko、Todo Yukiharu、Watari Hidemichi
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 38 Issue: 1 Pages: 295-310

    • DOI

      10.1186/s13046-019-1306-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ovarian Primary and Metastatic Tumors Suppressed by Survivin Knockout or a Novel Survivin Inhibitor2019

    • Author(s)
      Zhao Guannan、Wang Qinghui、Wu Zhongzhi、Tian Xinchun、Yan Huan、Wang Baojin、Dong Peixin、Watari Hidemichi、Pfeffer Lawrence M.、Guo Yuqi、Li Wei、Yue Junming
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 18 Issue: 12 Pages: 2233-2245

    • DOI

      10.1158/1535-7163.mct-19-0118

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy2019

    • Author(s)
      Asano Hiroshi、Hatanaka Kanako C.、Matsuoka Ryosuke、Dong Peixin、Mitamura Takashi、Konno Yosuke、Kato Tatsuya、Kobayashi Noriko、Ihira Kei、Nozaki Ayako、Oku Akira、Matsuno Yoshihiro、Hatanaka Yutaka、Watari Hidemichi
    • Journal Title

      Annals of Surgical Oncology

      Volume: ― Issue: 7 Pages: 2159-2168

    • DOI

      10.1245/s10434-019-08103-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation2019

    • Author(s)
      Xu Daozhi、Dong Peixin、Xiong Ying、Yue Junming、Ihira Kei、Konno Yosuke、Kobayashi Noriko、Todo Yukiharu、Watari Hidemichi
    • Journal Title

      Cancers

      Volume: 11 Issue: 8 Pages: 1130-1130

    • DOI

      10.3390/cancers11081130

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] PD-L1 is a tumor suppressor in aggressive endometrial cancer cells and its expression is regulated by miR-216a2021

    • Author(s)
      Daozhi Xu, Peixin Dong, Kei Ihira, Yosuke Konno and Hidemichi Watari
    • Organizer
      第73回日本産科婦人科学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] MicroRNA-361 directly targets HSP90 to repress EMT and invasion in cervical cancer cell2020

    • Author(s)
      .Daozhi Xu, Peixin Dong, Kei Ihira, Yosuke Konno and Hidemichi Watari
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] Long non-coding RNA NEAT1 drives aggressive endometrial cancer progression via sponging microRNA-3612020

    • Author(s)
      Peixin Dong, Daozhi Xu, Kei Ihira, Yosuke Konno and Hidemichi Watari
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] LncRNA NEAT1-mediated miR-361 downregulation contributes to EMT and sphere formation of cervical cancer cells via increasing HSP90 expression2020

    • Author(s)
      Peixin Dong, Daozhi Xu, Kei Ihira, Yosuke Konno and Hidemichi Watari
    • Organizer
      The 2020 xDigital Annual Global Meeting of the International Gynecologic Cancer Society
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 子宮頸癌悪性化におけるPD-L1の促進的役割の解明とその発現制御に関する基礎的検討2019

    • Author(s)
      董 培新
    • Organizer
      第28回日本癌病態治療研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Control of PD-L1 expression by miR-140/142/340/383 in cervical cancer2019

    • Author(s)
      DONG PEIXIN
    • Organizer
      The 2nd World Conference of Immuno-Oncology-2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] https://researchmap.jp/2853

    • Related Report
      2021 Annual Research Report
  • [Remarks] https://researchmap.jp/2853

    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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