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Genotype-dependent regulation of drug-metabolizing enzymes by microRNAs

Research Project

Project/Area Number 24390039
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionKanazawa University

Principal Investigator

NAKAJIMA Miki  金沢大学, 薬学系, 教授 (70266162)

Research Collaborator NAKANO Masataka  
IWAKAMI Chika  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsマイクロRNA / 遺伝子変異 / 個人差 / 転写後調節 / 薬物代謝酵素 / 薬物動態
Outline of Final Research Achievements

Genetic polymorphisms of drug-metabolizing enzymes are relevant to interindividual differences in pharmacokinetics, drug response and toxicity. Effects of SNPs in the coding region and 5’-UTR on enzyme activities or expression levels have been well studied, whereas SNPs in the 3’-UTR have been overlooked. Some SNPs in the 3’-UTR of concerned genes are associated with the change in the expression level. In this study, we found that human CYP2E1, AKR1D1, and TYMS are regulated by microRNA in the genotype-dependent manner. This is the first proof that a SNP(s) in the 3’-UTR of drug-metabolizing enzymes affects binding of miRNA to modulate the expression in the liver.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (27 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Invited: 4 results) Book (1 results) Remarks (1 results)

  • [Journal Article] CYP2A7 pseudogene transcript affects CYP2A6 expression in human liver by acting as a decoy for miR-126*.2015

    • Author(s)
      Masataka Nakano, Yasunari Fukushima, Shin-ichi Yokota, Tatsuki Fukami, Masataka Takamiya, Yasuhiro Aoki, Tsuyoshi Yokoi, and Miki Nakajima.
    • Journal Title

      Drug Metab. Dispos

      Volume: 43 Issue: 5 Pages: 703-712

    • DOI

      10.1124/dmd.115.063255

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Changes in the expression of miRNAs at the pericentral and periportal regions of the rat liver in response to hepatocellular injury: comparison with the changes in the expression of plasma miRNAs.2014

    • Author(s)
      Yu Yamaura, Miki Nakajima, Naoyuki Tatsumi, Shingo Takagi, Tatsuki Fukami, Koichi Tsuneyama, and Tsuyoshi Yokoi.
    • Journal Title

      Toxicology

      Volume: 322 Pages: 89-98

    • DOI

      10.1016/j.tox.2014.05.008

    • NAID

      120005596361

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retinoid X receptor α in human liver is regulated by miR-34a.2014

    • Author(s)
      Yuki Oda, Miki Nakajima, Koichi Tsuneyama, Masataka Takamiya, Yasuhiro Aoki, Tatsuki Fukami, and Tsuyoshi Yokoi.
    • Journal Title

      Biochem. Pharmacol.

      Volume: 90 Issue: 2 Pages: 179-187

    • DOI

      10.1016/j.bcp.2014.05.002

    • NAID

      120005596359

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of cytochrome b5 expression by miR-223 in human liver: effects on cytochrome P450 activities.2014

    • Author(s)
      Kei Takahashi, Yuki Oda, Yasuyuki Toyoda, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima.
    • Journal Title

      Pharm. Res.

      Volume: 31 Issue: 3 Pages: 780-794

    • DOI

      10.1007/s11095-013-1200-7

    • NAID

      120005596360

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated Analysis of Rifampicin-induced MicroRNA and Gene Expression Changes in Human Hepatocytes2014

    • Author(s)
      Kei Takahashi, Naoyuki Tatsumi, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima.
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 29 Issue: 4 Pages: 333-340

    • DOI

      10.2133/dmpk.DMPK-13-RG-114

    • NAID

      130004463394

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 薬・異物や生体内化合物の代謝を制御するmicroRNA2013

    • Author(s)
      中島美紀
    • Journal Title

      昭和大学薬学雑誌

      Volume: 4 Pages: 1-11

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] microRNAs as mediators of drug toxicity2013

    • Author(s)
      Yokoi T, Nakajima M
    • Journal Title

      Annu. Rev. Pharmacol. Toxicol.

      Volume: 53 Issue: 1 Pages: 377-400

    • DOI

      10.1146/annurev-pharmtox-011112-140250

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 3’-UTRのSNPによるヒトAKR1D1の発現変動の原因となるmicroRNAの解明2015

    • Author(s)
      岩上智香、深見達基、中島美紀
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      神戸学院大学等(神戸)
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNAによるヒトUGT1Aの発現制御解析:薬物のグルクロン酸抱合活性への影響2014

    • Author(s)
      辰巳直之、深見達基、中島美紀
    • Organizer
      日本薬学会北陸支部総会第126回例会
    • Place of Presentation
      金沢大学(金沢)
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒトAKR1D1の遺伝子型特異的なmicroRNAによる発現制御2014

    • Author(s)
      岩上智香、深見達基、中島美紀
    • Organizer
      日本薬学会北陸支部総会第126回例会
    • Place of Presentation
      金沢大学(金沢)
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNA-related polymorphisms to predict drug response.2014

    • Author(s)
      Miki Nakajima
    • Organizer
      19th North American Regional ISSX Meeting/29th JSSX Annual Meeting.
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-10-18 – 2014-10-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ヒトCYP2A6のmiRNAによる発現制御に与える偽遺伝子CYP2A7の影響2014

    • Author(s)
      中野正隆、福島靖也、横田真一、横井 毅、中島美紀
    • Organizer
      第6回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島(広島)
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] CYP2A7 pseudogene transcript affects CYP2A6 expression by acting as a decoy for microRNA binding.2014

    • Author(s)
      Masataka Nakano, Yasunari Fukushima, Shin-ichi Yokota, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima
    • Organizer
      20th International Symposium on Microsomes and Drug Oxidations
    • Place of Presentation
      Stuttgart, Germany
    • Year and Date
      2014-05-18 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] New knowledge of microRNAs controlling human P450 expression or activities.2014

    • Author(s)
      Miki Nakajima
    • Organizer
      5th Asia Pacific ISSX Meeting
    • Place of Presentation
      Tianjin, China
    • Year and Date
      2014-05-09 – 2014-05-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 薬によるmicroRNAの発現変動と薬効・副作用予測2014

    • Author(s)
      中島美紀
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 肝疾患患者の血中microRNAプロファイルを用いた病型診断法の検討2013

    • Author(s)
      中島美紀、山浦優、辰巳直之、高木信伍、深見達基、常山幸一、田尻和人、峯村正実、横井毅
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Annual Research Report
  • [Presentation] NAFLDの進行に関与する肝臓中microRNAsの解析:モデルラットを用いた検討2013

    • Author(s)
      辰巳直之、中島美紀、山浦優、深見達基、常山幸一、横井 毅
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒトCYP2E1 3’-UTR上のSNPがmiR-570結合性およびヒト肝におけるCYP2E1発現量に与える影響2013

    • Author(s)
      中野正隆、茂利拓也、深見達基、横井 毅、中島美紀
    • Organizer
      第5回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島(広島)
    • Related Report
      2013 Annual Research Report
  • [Presentation] miR-34aによるヒトretinoid X receptor aの発現制御は肝線維化の進行の一因となる2013

    • Author(s)
      小田祐輝、中島美紀、深見達基、横井 毅
    • Organizer
      第5回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島(広島)
    • Related Report
      2013 Annual Research Report
  • [Presentation] New knowledge of the microRNA-mediated regulation of drug metabolism2013

    • Author(s)
      Nakajima M
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      タワーホール船堀 (東京)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Allele specific regulation of human CYP2E1 by a microRNA.2013

    • Author(s)
      Nakano M, Mohri T, Fukami T, Yokoi T, Nakajima M.
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      タワーホール船堀 (東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Control of xeno/endobiotics-metabolizing P450s by microRNAs2012

    • Author(s)
      Nakajima M
    • Organizer
      チトクロムP450発見50周年記念シンポジウム
    • Place of Presentation
      九州大学(福岡)(招待講演)
    • Year and Date
      2012-12-03
    • Related Report
      2012 Annual Research Report
  • [Presentation] Role of microRNA in human CYP2A6 regulation2012

    • Author(s)
      Nakano M, Nakajima M, Fukushima Y, Yokota S, Fukami T, Yokoi T.
    • Organizer
      チトクロムP450発見50周年記念シンポジウム
    • Place of Presentation
      九州大学(福岡)
    • Year and Date
      2012-12-03
    • Related Report
      2012 Annual Research Report
  • [Presentation] Role of microRNA in human CYP2A6 regulation2012

    • Author(s)
      Nakano M, Nakajima M, Fukushima Y, Yokota S, Fukami T, Yokoi T.
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2012-11-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Human CYP2A6 is regulated by miR-1262012

    • Author(s)
      Nakano M, Nakajima M, Fukushima Y, Yokota S, Fukami T, Yokoi T.
    • Organizer
      18th North American Regional Meeting
    • Place of Presentation
      Hilton Anatole Dallas Hotel(USA)
    • Year and Date
      2012-10-14
    • Related Report
      2012 Annual Research Report
  • [Book] 異物代謝酵素のマイクロRNAによる制御「毒性の科学―分子・細胞から人間集団まで」2014

    • Author(s)
      熊谷嘉人、姫野誠一郎、渡辺知保、中島美紀、他
    • Total Pages
      200
    • Publisher
      東京大学出版会
    • Related Report
      2013 Annual Research Report
  • [Remarks] 金沢大学医薬保健研究域薬物代謝安全性学研究室ウェブページ

    • URL

      http://www.p.kanazawa-u.ac.jp/~taisha/index.html

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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