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RNA epigenetics regulation by ABH family and regulation failure mechanism in cancer

Research Project

Project/Area Number 26293015
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionOsaka University

Principal Investigator

TSUJIKAWA KAZUTAKE  大阪大学, 薬学研究科(研究院), 教授 (10207376)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
KeywordsRNAエピジェネティクス / ABHファミリー / ALKBH / 癌 / エピジェネティクス / がん / RNA / 脱メチル化 / 薬学
Outline of Final Research Achievements

AlkB homolog 3 (ABH3, ALKBH3), which is originally designated as prostate cancer antigen-1, is highly expressed in prostate cancer, pancreatic cancer, and non-small-cell lung cancer. ALKBH3 catalyzes the demethylation of 1-methyladenine (1-meA), 3-methylcytosine (3-meC), and N6-methyladenine (N6-meA) in DNA and RNA. In this study, ALKBH3 was found to effectively demethylate 1-meA, 3-meC, and N6-meA within endogenously methylated RNA. An in vitro translation assay showed that ALKBH3-demethylated tRNA significantly enhanced protein translation efficiency. In addition, ALKBH3 knockdown in Panc-1 cells suppressed the nascent protein synthesis. Thus, our data highlight a novel role for ALKBH3 in tumor progression via RNA demethylation and subsequent protein synthesis promotion. Moreover, ALKBH family molecules were found to demethylate specific methylated bases in RNA. These results open a new avenue for RNA epigenetic regulation by ALKBH family molecules.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (19 results)

All 2017 2016 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Invited: 1 results) Book (1 results) Remarks (3 results)

  • [Journal Article] AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells.2017

    • Author(s)
      Ueda Y, Ooshio I, Fusamae Y, Kitae K, Kawaguchi M, Jingushi K, Hase H, Harada K, Hirata K, Tsujikawa K.
    • Journal Title

      Sci Rep. 2017 Feb 13;7:42271.

      Volume: 13 Issue: 1 Pages: 42271-42271

    • DOI

      10.1038/srep42271

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A real-time PCR-based quantitative assay for 3-methylcytosine demethylase activity of ALKBH32016

    • Author(s)
      Ueda Y ,Kitae K, Ooshio I, Fusamae Y, Kawaguchi M, Jingushi K, Harada K, Hirata K, Tsujikawa K.
    • Journal Title

      Biochem. Biophys. Rep.

      Volume: 5 Pages: 476-481

    • DOI

      10.1016/j.bbrep.2016.02.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ALKBH6 によるRNA メチル化制御の検討2017

    • Author(s)
      長谷 拓明, 大塩 郁幹, 上田 裕子, 北惠 郁緒里, 木本 瑞基, 西本 愛, 犬伏 智子, 辻川 和丈
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] RNA epigenetics解析と膀胱癌におけるRNA修飾酵素AlkB homolog 8の機能2017

    • Author(s)
      大塩 郁幹,上田 裕子,長谷 拓明,北惠 郁緒里,神宮司 健太郎,島ノ 江知樹, 趙 雨桐,里 章平,藤井 晋太郎,藤田 和利,植村 元秀,野々村 祝夫,辻川 和丈
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] がん細胞におけるAlkB homolog 3 (ALKBH3)によるRNAメチル化修飾制御の意義2016

    • Author(s)
      上田 裕子,大塩 郁幹,長谷 拓明,北恵 郁緒里,河口 恵,小垣 考弘,神宮司 健太郎,辻川 和丈
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] RNA epigenetics による生体制御の基盤的研究2016

    • Author(s)
      長谷 拓明, 大塩 郁幹, 上田 裕子, 北惠 郁緒里, 西本 愛, 犬伏 智子, 木本 瑞基, 古川 龍彦, 辻川 和丈
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] エピトランスクリプトームとがん2016

    • Author(s)
      辻󠄀川和丈
    • Organizer
      第4回がんと代謝
    • Place of Presentation
      かごしま県民交流センター
    • Year and Date
      2016-07-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 非小細胞肺癌細胞におけるABH3のDNA脱メチル化機能解析2016

    • Author(s)
      小垣考弘、仲井秀一、大塩郁幹、河口恵、西本愛、北恵郁緒里、小林巧明、神宮司健太郎、上田裕子、深田宗一郎、辻川和丈
    • Organizer
      日本薬学会136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] ABH3によるRNA脱メチル化制御の破綻が膵癌の進行に寄与する2015

    • Author(s)
      上田裕子,川上竜司,神宮司健太郎,古川龍彦,辻川和丈
    • Organizer
      第19回日本がん分子標的治療学会学術集会
    • Place of Presentation
      松山全日空ホテル(愛媛県松山市)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] ABH3のRNA脱メチル化を介したタンパク質翻訳制御機構の解明2015

    • Author(s)
      河口恵, 上田裕子, 北惠郁緒里, 仲井秀一, 大塩郁幹, 小林巧明, 神宮司健太郎, 深田宗一朗, 青木俊二, 馬淵美雪, 田中明人, 辻川和丈
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ABH3のDNA脱メチル化酵素活性制御による非小細胞肺癌細胞の表現型解析2015

    • Author(s)
      仲井秀一 大塩郁幹、河口恵、上田裕子、北惠郁緖里、小林巧明、神宮司健太郎、深田宗一朗、辻川和丈
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ABH family分子によるRNAエピジェネティクス制御2015

    • Author(s)
      大塩 郁幹,上田 裕子, 北惠 郁緒里, 河口 恵, 仲井 秀一,深田 宗一朗, 原田 和生,平田 収正, 辻川 和丈
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] AlkB homolog 8 (ABH8)のノックダウンにより膀胱癌細胞に誘導されるアポトーシス経路の解明2014

    • Author(s)
      川上竜司,塚田陽平,北惠郁緒里,神宮司健太郎,上田裕子,辻川和丈
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膀胱癌で高発現するAlkB homolog 8 ( ABH8 ) のアポトーシス抑制機構の解析2014

    • Author(s)
      塚田陽平、川上竜司、北惠郁緒里、神宮司健太郎、上田裕子、深田宗一朗、中田渡、藤田和利、植村元秀、野々村祝夫、辻川和丈
    • Organizer
      第64回 日本薬学会 近畿支部総会・大会
    • Place of Presentation
      京都薬科大学(京都)
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膀胱癌で高発現する AlkB homolog 8 (ABH8) の機能解析と核酸医薬の創製2014

    • Author(s)
      川上竜司,塚田陽平,中嶋一裕,北恵郁緒里,中田 渡,藤田和利,植村元秀,神宮司健太郎,上田裕子, 野々村祝夫,辻川和丈
    • Organizer
      第6回 日本RNAi研究会
    • Place of Presentation
      広島グランドプリンスホテル(広島)
    • Year and Date
      2014-08-29
    • Related Report
      2014 Annual Research Report
  • [Book] Regulation of RNA methylation and epigeneticis effects by the ALKBH family2016

    • Author(s)
      辻川 和丈
    • Total Pages
      6
    • Publisher
      日本生化学会
    • Related Report
      2016 Annual Research Report
  • [Remarks] ALKBHファミリー分子

    • URL

      https://sites.google.com/site/xibaoshengli/alkbhfam

    • Related Report
      2016 Annual Research Report
  • [Remarks] ALKBHファミリー分子

    • URL

      https://sites.google.com/site/xibaoshengli/alkbhfamiri-fen-zi

    • Related Report
      2015 Annual Research Report
  • [Remarks] ABHグループ

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b008/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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