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Identification of the upstream regulatory genes specific to the subtypes of uterine leiomyoma without the MED12 mutation

Research Project

Project/Area Number 18K09262
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 InstitutionYamaguchi University

Principal Investigator

SATO Shun  山口大学, 大学院医学系研究科, 助教 (10534604)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords子宮筋腫 / MED12突然変異 / 筋腫サブタイプ / MED12変異 / 遺伝子発現 / 発生・進展
Outline of Final Research Achievements

To clarify the specificity and commonality between the MED12-mut and MED12-wt uterine leiomyoma subtypes, based on the mRNA expression data, the aberrant expressed genes in each leiomyoma subtype and the co-expressed genes by the weighted gene co-expression network analysis were identified. The pathway analysis for the identified aberrant expressed genes and co-expressed genes revealed that the signaling pathways involving the extracellular matrix production and the angiogenesis are activated, in MED12-mut and MED12-wt leiomyoma subtypes, respectively. In addition, SATB2 and NRG1, which are involved in the onset and development of MED12-mut leiomyomas, are also highly expressed in the most MED12-wt leiomyoma specimens, suggesting that these genes may function in common in both leiomyoma subtypes. The findings in the study will be the basis for providing appropriate treatments for the patients bearing each leiomyoma subtype.

Academic Significance and Societal Importance of the Research Achievements

現在,子宮筋腫の根治には子宮摘出等の外科的手術が必要であり,子宮温存に有効な治療薬が求められている。効果が期待される治療薬の1つにプロゲステロン受容体調節剤があるが,既に実用化されている欧米では効果に個人差が報告されており,この効果の差異に個人が有する筋腫の種類(MED12(+)筋腫あるいはMED12(-)筋腫)が関与する可能性がある。本研究の成果であるMED12(+)筋腫とMED12(-)筋腫の特異性および共通性の知見は,患者の有する筋腫の種類により子宮温存を考慮した適切な治療を提供するための基礎となるので,少子化問題を抱える本邦にとっては社会的にも意義が大きい。

Report

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

    (22 results)

All 2021 2020 2019 2018

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 11 results) Presentation (7 results) (of which Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells2021

    • Author(s)
      Tamura Isao、Maekawa Ryo、Jozaki Kosuke、Ohkawa Yasuyuki、Takagi Haruka、Doi-Tanaka Yumiko、Shirafuta Yuichiro、Mihara Yumiko、Taketani Toshiaki、Sato Shun、Tamura Hiroshi、Sugino Norihiro
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 520 Pages: 111085-111085

    • DOI

      10.1016/j.mce.2020.111085

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Integrated Genomic Approach Identifies HOXC8 as an Upstream Regulator in Ovarian Endometrioma2020

    • Author(s)
      Yumiko Mihara, Ryo Maekawa, Shun Sato, Natsuko Shimizu, Yumiko Doi-Tanaka, Haruka Takagi, Yuichiro Shirafuta, Masahiro Shinagawa, Isao Tamura, Toshiaki Taketani, Hiroshi Tamura, Takeshi Abe, Yoshiyuki Asai, Norihiro Sugino
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 105 Issue: 12 Pages: 1-12

    • DOI

      10.1210/clinem/dgaa618

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes2020

    • Author(s)
      Kagawa Y, Umaru BA, Shima H, Ito R, Zama R, Islam A, Kanno S, Yasui A, Sato S, Jozaki K, Shil SK, Miyazaki H, Kobayashi S, Yamamoto Y, Kogo H, Shimamoto-Mitsuyama C, Sugawara A, Sugino N, Kanamori M, Tominaga T, Yoshikawa T, Fukunaga K, Igarashi K, Owada Y
    • Journal Title

      Molecular Neurobiology

      Volume: 57 Issue: 12 Pages: 4891-4910

    • DOI

      10.1007/s12035-020-02057-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of aberrantly expressed long non‐coding RNAs in ovarian high‐grade serous carcinoma cells2020

    • Author(s)
      Nakashima Kengo、Sato Shun、Tamura Isao、Hayashi‐Okada Maki、Tamehisa Tetsuro、Kajimura Takuya、Sueoka Kotaro、Sugino Norihiro
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 19 Issue: 3 Pages: 277-285

    • DOI

      10.1002/rmb2.12330

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Wilms tumor 1 regulates lipid accumulation in human endometrial stromal cells during decidualization2020

    • Author(s)
      Tamura Isao、Takagi Haruka、Doi-Tanaka Yumiko、Shirafuta Yuichiro、Mihara Yumiko、Shinagawa Masahiro、Maekawa Ryo、Taketani Toshiaki、Sato Shun、Tamura Hiroshi、Sugino Norihiro
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press Issue: 14 Pages: 4673-4683

    • DOI

      10.1074/jbc.ra120.012841

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging2020

    • Author(s)
      Tamura Hiroshi、Jozaki Mai、Tanabe Manabu、Shirafuta Yuichiro、Mihara Yumiko、Shinagawa Masahiro、Tamura Isao、Maekawa Ryo、Sato Shun、Taketani Toshiaki、Takasaki Akihisa、Reiter Russel J.、Sugino Norihiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 3 Pages: 1135-1135

    • DOI

      10.3390/ijms21031135

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas.2020

    • Author(s)
      Shun Sato , Ryo Maekawa , Isao Tamura , Yuichiro Shirafuta , Masahiro Shinagawa , Hiromi Asada , Toshiaki Taketani , Hiroshi Tamura , Norihiro Sugino
    • Journal Title

      Journal of assisted reproduction and genetics

      Volume: 36 Issue: 11 Pages: 2385-2397

    • DOI

      10.1007/s10815-019-01582-y

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of carbonyl reductase 1 inhibits malignant behaviors and epithelial mesenchymal transition by suppressing TGF-β signaling in uterine leiomyosarcoma cells2019

    • Author(s)
      Kajimura Takuya、Sato Shun、Murakami Akihiro、Hayashi-Okada Maki、Nakashima Kengo、Sueoka Kotaro、Sugino Norihiro
    • Journal Title

      Oncology Letters

      Volume: 18 Pages: 1503-1512

    • DOI

      10.3892/ol.2019.10429

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose regulates the histone acetylation of gene promoters in decidualizing stromal cells2019

    • Author(s)
      Jozaki Kosuke、Tamura Isao、Takagi Haruka、Shirafuta Yuichiro、Mihara Yumiko、Shinagawa Masahiro、Maekawa Ryo、Taketani Toshiaki、Asada Hiromi、Sato Shun、Tamura Hiroshi、Sugino Norihiro
    • Journal Title

      Reproduction

      Volume: 157 Issue: 5 Pages: 457-464

    • DOI

      10.1530/rep-18-0393

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genome-wide DNA methylation analysis revealed stable DNA methylation status during decidualization in human endometrial stromal cells2019

    • Author(s)
      Maekawa Ryo、Tamura Isao、Shinagawa Masahiro、Mihara Yumiko、Sato Shun、Okada Maki、Taketani Toshiaki、Tamura Hiroshi、Sugino Norihiro
    • Journal Title

      BMC Genomics

      Volume: 20 Issue: 1 Pages: 324-324

    • DOI

      10.1186/s12864-019-5695-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma2019

    • Author(s)
      Maekawa Ryo、Mihara Yumiko、Sato Shun、Okada Maki、Tamura Isao、Shinagawa Masahiro、Shirafuta Yuichiro、Takagi Haruka、Taketani Toshiaki、Tamura Hiroshi、Sugino Norihiro
    • Journal Title

      Journal of Ovarian Research

      Volume: 12 Issue: 1

    • DOI

      10.1186/s13048-019-0489-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] C/EBPβ regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats2019

    • Author(s)
      Shinagawa Masahiro、Tamura Isao、Maekawa Ryo、Sato Shun、Shirafuta Yuichiro、Mihara Yumiko、Okada - Matsumoto Maki、Taketani Toshiaki、Asada Hiromi、Tamura Hiroshi、Sugino Norihiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-018-36566-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The distal upstream region of insulin-like growth factor-binding protein-1 enhances its expression in endometrial stromal cells during decidualization2018

    • Author(s)
      Tamura I, Jozaki K, Sato S, Shirafuta Y, Shinagawa M, Maekawa R, Taketani T, Asada H, Tamura H, Sugino N.
    • Journal Title

      J Biol Chem

      Volume: 293 Issue: 14 Pages: 5270-5280

    • DOI

      10.1074/jbc.ra117.000234

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Different DNA methylation profiles between MED12 mutation-positive and -negative uterine leiomyomas.2020

    • Author(s)
      Maekawa R, Sato S, Mihara Y, Shinagawa M, Tamura I, Taketani T, Takagi H, Tanaka Y, Shirafuta Y, Shimizu N, Tamura H, Sugino N.
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] SATB2 および NRG1 の子宮筋腫の発生・進展における上流の制御因子としての役割2020

    • Author(s)
      佐藤 俊・前川 亮・田村 功・白蓋雄一郎・品川征大・竹谷俊明・田村博史・杉野法広
    • Organizer
      第24回日本生殖内分泌学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] DNAメチル化を基盤とした病態解明とバイオマーカーの開発2019

    • Author(s)
      佐藤俊、前川亮、杉野法広
    • Organizer
      第29回日本内分泌学会臨床内分泌代謝Update
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Identification of specific long non-coding RNA (lncRNA) in ovarian high grade serous carcinoma (HGSC)2019

    • Author(s)
      NAKASHIMA Kengo, SATO Shun, HAYASHI-OKADA Maki, KAJIMURA Takuya, TAKETANI Toshiaki, SUEOKA Kotaro, SUGINO Norihiro
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] SATB2およびNRG1遺伝子の子宮筋腫の発生・進展における上流の制御因子としての役割2018

    • Author(s)
      佐藤俊、前川亮、田村功、白蓋雄一郎、品川征大、浅田裕美、竹谷俊明、田村博史、杉野法広
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 子宮筋腫の発生・進展におけるSATB2およびNRG1遺伝子の関与2018

    • Author(s)
      前川亮、佐藤俊、田村功、品川征大、三原由実子、高木遥香、土井結美子、松本真紀、竹谷俊明、田村博史、杉野法広
    • Organizer
      第28回臨床内分泌Update
    • Related Report
      2018 Research-status Report
  • [Presentation] HOXC8の卵巣チョコレート嚢腫における発症・伸展への関与2018

    • Author(s)
      前川亮、佐藤俊、三原由美子、品川征大、田村功、高木遥香、竹谷俊明、松本真紀、田村博史、杉野法広
    • Organizer
      第12回エピジェネティクス研究会
    • Related Report
      2018 Research-status Report
  • [Book] Biomarker of uterine fibroids. Uterine fibroids and adenomyosis, edited by Sugino N.2018

    • Author(s)
      Sato Shun, Sugino Norihiro.
    • Total Pages
      17
    • Publisher
      Springer co. Ltd.
    • ISBN
      9789811071669
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 子宮平滑筋における腫瘍の診断マーカー2018

    • Inventor(s)
      佐藤俊 , 杉野法広
    • Industrial Property Rights Holder
      国立大学法人山口大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Acquisition Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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