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Regulatory system of RNA methylation in malignant brain tumors

Research Project

Project/Area Number 17K10867
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKochi University

Principal Investigator

Ueba Tetsuya  高知大学, 教育研究部医療学系臨床医学部門, 教授 (00314203)

Co-Investigator(Kenkyū-buntansha) 八幡 俊男  高知大学, 教育研究部医療学系臨床医学部門, 助教 (40380323)
川西 裕  高知大学, 教育研究部医療学系臨床医学部門, 助教 (90527582)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords膠芽腫 / RNA修飾 / RNAメチル化 / 幹細胞 / RNA / 核酸の修飾 / RNA methylation / Brain tumor
Outline of Final Research Achievements

Current knowledge of RNA cytosine methylation is still poor in malignant glioma. In this study, we aimed the investigation of methylation level in RNA and the search for the regulatory genes. DNA demethylase TET genes were involved with regulation of RNA methylation in glioblastoma. Alteration of RNA methylation levels were observed in glioblastoma and oligodendroglioma tissues. Several genes were identified that regulated RNA methylation and affected cell proliferation. Furthermore, it was suggested that TET3 may play a role for regulation of cell differentiation in glioblastoma. This study shows linkage of malignant brain tumor and aberration of RNA modification.

Academic Significance and Societal Importance of the Research Achievements

DNAのエピジェネティックな修飾に関する研究は精力的に行われているが、RNAの修飾に関しては限られている。RNAのシトシンメチル化が転写後のRNAの寿命や翻訳効率に関わる可能性が示唆されているが、生物学的意義は十分に検討されていない。本研究において、脳腫瘍におけるRNAメチル化量の異常が検出されたことは、RNAの修飾が脳の機能に限局せず、細胞のがん形質や発がんに関与する可能性を示唆している。がん幹細胞を用いて検討することで、RNA修飾の膠芽腫における本質的な機能を見出すことが出来た。将来的には、極めて予後の悪い膠芽腫に対する新規治療に有用なRNA標的分子の同定が期待可能である。

Report

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

    (12 results)

All 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (5 results)

  • [Journal Article] CD146 is highly expressed in glioma stem cells and acts as a cell cycle regulator2019

    • Author(s)
      Yawata Toshio、Higashi Youichiro、Kawanishi Yu、Nakajo Takahito、Fukui Naoki、Fukuda Hitoshi、Ueba Tetsuya
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 144 Issue: 1 Pages: 21-32

    • DOI

      10.1007/s11060-019-03200-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient delivery of small interfering RNAs targeting particular mRNAs into pancreatic cancer cells inhibits invasiveness and metastasis of pancreatic tumors2019

    • Author(s)
      Taniuchi Keisuke、Yawata Toshio、Tsuboi Makiko、Ueba Tetsuya、Saibara Toshiji
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 30 Pages: 2869-2886

    • DOI

      10.18632/oncotarget.26880

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Remote effects in the ipsilateral thalamus and/or contralateral cerebellar hemisphere using FDG PET in patients with brain tumors.2018

    • Author(s)
      Iwasa H, Murata Y, Nishimori M, Miyatake K, Tadokoro M, Kohsaki S, Nogami M, Ueba Y, Ueba T, Yamagami T.
    • Journal Title

      Jpn J Radiol

      Volume: 36 Issue: 4 Pages: 303-311

    • DOI

      10.1007/s11604-018-0721-8

    • NAID

      210000173243

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stimulation of brain nicotinic acetylcholine receptors activates adrenomedullary outflow via brain inducible NO synthase-mediated S-nitrosylation2018

    • Author(s)
      Higashi Y, Shimizu T, Yamamoto M, Tanaka K, Yawata T, Shimizu S, Zou S, Ueba T, Yuri K, Saito M.
    • Journal Title

      Br J Pharmacol.

      Volume: 175 Issue: 19 Pages: 3758-3772

    • DOI

      10.1111/bph.14445

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The inhibitory role of intracellular free zinc in the regulation of Arg-1 expression in interleukin-4-induced activation of M2 microglia.2018

    • Author(s)
      Aratake T, Higashi Y, Ueba Y, Hamada T, Shimizu T, Shimizu S, Yawata T, Ueba T, Saito M.
    • Journal Title

      Metallomics

      Volume: 10 Issue: 10 Pages: 1501-1509

    • DOI

      10.1039/c8mt00248g

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Attenuation of zinc-enhanced inflammatory M1 phenotype of microglia by peridinin protects against short-term spatial-memory impairment following cerebral ischemia in mice.2018

    • Author(s)
      Ueba Y, Aratake T, Onodera KI, Higashi Y, Hamada T, Shimizu T, Shimizu S, Yawata T, Nakamura R, Akizawa T, Ueba T, Saito M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 507 Issue: 1-4 Pages: 476-483

    • DOI

      10.1016/j.bbrc.2018.11.067

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.2018

    • Author(s)
      Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T, Kanamori M, Nagane M, Kumabe T, Hirose Y, Ichikawa T, Kobayashi H, Fujimaki T, Goto H, Takeshima H, Ueba T, Abe H, Tamiya T, Sonoda Y, Natsume A, Kakuma T, Sugita Y, Komatsu N, Yamada A, Sasada T, Matsueda S, Shichijo S, Itoh K, Terasaki M.
    • Journal Title

      Neuro Oncol.

      Volume: 21 Issue: 3 Pages: 348-359

    • DOI

      10.1093/neuonc/noy200

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膠芽腫幹細胞で高発現するCD146を標的とした治療法の開発2019

    • Author(s)
      八幡俊男、福井直樹、川西 裕、中城 登仁、上羽 哲也
    • Organizer
      日本脳腫瘍学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膠芽腫幹細胞で高発現するCD146の治療標的としての有用性の検討2019

    • Author(s)
      福井 直樹、八幡 俊男、上羽 佑亮、川西 裕、門田 知倫、木田 波斗、松岡 渓太、山崎 大智、道上 怜奈、濱田 史泰、野中 大 伸、中居 永一、岡田 憲二、福田 仁、中城 登仁、上羽 哲也
    • Organizer
      日本脳神経外科学会第78回学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膠芽腫幹細胞で高発現するCD146の治療標的としての有用性の検討2019

    • Author(s)
      福井 直樹、八幡 俊男、川西 裕、福田 仁、門田 知倫、岡田 憲二、濵田 史泰、道上 玲奈、 木田 波斗、松岡 渓太、山﨑 大智、野中 大伸、中居 永一、中城 登仁、上羽 哲也
    • Organizer
      日本分子脳神経外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 初発悪性神経膠腫に対するWT1-W10免疫療法2019

    • Author(s)
      川西 裕、宇高 恵子、八幡 俊男、中居 永一、福田 仁、福井 直樹、上羽 哲也
    • Organizer
      日本脳神経外科学会第78回学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 初発悪性神経膠腫に対するWT1-W10免疫療法2019

    • Author(s)
      川西 裕, 宇高 恵子, 土肥 俊, 八幡 俊男, 中居 永一, 福田 仁, 福井 直樹, 上羽 哲也
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Annual Research Report

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

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