microRNA reguIating human drug metaboIism : innovative study for the interindividual variability

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390043
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: NAKAJIMA Miki 金沢大学, 薬学系, 准教授 (70266162)
• Project Period (FY): 2009 – 2011
• Keywords: マイクロRNA / 転写後調節 / 核内レセプター / シトクロムP450 / 個人差

Research Abstract

We found that the expression of HNF4α, PPARα, and ARNT in human liver is regulated by miRNAs. The miRNA? dependent regulation of these transcription factors affects the expression of their downstream genes, being a crucial factor of interindividual variability of drug metabolism, bile acid synthesis, lipid metabolism, detoxification of xenobiotics, and response to stimuli.

Research Products

• [Journal Article] Aryl hydrocarbon receptor nuclear translocator in human livers is regulated by miR-24 (2012)
  • Author(s): Oda Y, Nakajima M, Mohri T, Takamiya M, Aoki Y, Fukami T, Yokoi T
  • Journal Title: Toxicol. Appl. Pharmacol. Volume: 260 Pages: 222-231
  • DOI: doi:10.1016/j.taap.2012.02.012
  • Peer Reviewed
• [Journal Article] Toxicological implications of modulation of gene expression by microRNAs (2011)
  • Author(s): Yokoi T, Nakajima M
  • Journal Title: Toxicol. Sci. Volume: 123 Pages: 1-14
  • DOI: doi:10.1093/toxsci/kfr168
  • Peer Reviewed
• [Journal Article] MicroRNAs from biology to future pharmacotherapy : regulation of cytochrome P450s and nuclear receptors (2011)
  • Author(s): Nakajima M, Yokoi T
  • Journal Title: Pharmacol. Ther. Volume: 131 Pages: 330-337
  • DOI: doi:10.1016/j.pharmthera.2011.04.009
  • Peer Reviewed
• [Journal Article] PPARa is regulated by miR-21 and miR-27b in human liver (2011)
  • Author(s): Kida K, Nakajima M, Mohri T, Oda Y, Takagi S, Fukami T, Yokoi T
  • Journal Title: Pharma. Res. Volume: 28 Pages: 2467-2476
  • DOI: doi:10.1007/s11095-011-0473-y
  • Peer Reviewed
• [Journal Article] シトクロムP450と転写因子のmicroRNAによる発現制御 (2011)
  • Author(s): 中島美紀
  • Journal Title: 薬学雑誌 Volume: 132 Pages: 107-116
  • DOI: doi:10.1248/yakushi.132.107
  • Peer Reviewed
• [Journal Article] MicroRNAs regulate human hepatocyte nuclear factor 4 a, modulating the expression of metabolic enzymes and cell cycle (2010)
  • Author(s): Takagi S, Nakajima M, Kida K, Yamaura Y, Fukami T, Yokoi T
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 4415-4422
  • DOI: doi:10.1074/jbc.M109.085431
  • Peer Reviewed
• [Journal Article] Human CYP2E1 is regulated by miR-378 (2010)
  • Author(s): Mohri T, Nakajima M, Fukami T, Takamiya M, Aoki Y, Yokoi T
  • Journal Title: Biochem. Pharmacol. Volume: 79 Pages: 1045-1052
  • DOI: doi:10.1016/j.bcp.2009.11.015
  • Peer Reviewed
• [Journal Article] Human CYP24 catalyzing the inactivation of calcitriol is post-transcriptionally regulated by miR-125b (2009)
  • Author(s): Komagata S, Nakajima M, Takagi S, Mohri T, Taniya T, Yokoi T
  • Journal Title: Mol. Pharmacol. Volume: 76 Pages: 702-709
  • DOI: doi:10.1124/mol.109.056986
  • Peer Reviewed
• [Journal Article] MicroRNA regulates human vitamin D receptor (2009)
  • Author(s): Mohri T, Nakajima M, Takagi S, Komagata S, Yokoi T
  • Journal Title: Int. J. Cancer Volume: 125 Pages: 1328-1333
  • DOI: doi:10.1002/ijc.24459
  • Peer Reviewed
• [Presentation] マイクロRNA :毒性学・異物代謝研究の新展開 (2011)
  • Author(s): 中島美紀
  • Organizer: フォーラム:衛生薬学・環境トキシコロジー
  • Place of Presentation: 金沢エクセルホテル東急(石川県)
  • Year and Date: 2011-10-28
• [Presentation] 薬物動態とmicroRNAの働き (2011)
  • Author(s): 中島美紀
  • Organizer: 第319回CBI学会研究講演会
  • Place of Presentation: 東京大学山上会館(東京都)
  • Year and Date: 2011-08-26
• [Presentation] 物動態におけるmicroRNAの役割とmicroRNAの発現変動 (2011)
  • Author(s): 中島美紀
  • Organizer: 第38回日本トキシコロジー学会学術年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-07-11
• [Presentation] マイクロRNAの薬物動態への関与と新規毒性評価への展望 (2011)
  • Author(s): 中島美紀
  • Organizer: 第25回日本薬物動態学会ワークショップ
  • Place of Presentation: 東京大学鉄門講堂(東京都)
  • Year and Date: 2011-05-12
• [Presentation] Regulation of human cytochrome P450s and nuclear receptors by microRNAs (2011)
  • Author(s): Nakajima M, Yokoi T
  • Organizer: 4th Asia Pacific International Society for Study of Xenobiotics Meeting
  • Place of Presentation: 国立成功大学(台湾)
  • Year and Date: 2011-04-22
• [Presentation] MiRNAの基礎と毒性研究 (2010)
  • Author(s): 中島美紀
  • Organizer: 第4回応用トキシコロジーリカレント講座
  • Place of Presentation: 金沢大学サテライトプラザ(石川県)
  • Year and Date: 2010-09-30
• [Presentation] MicroRNA regulation of nuclear receptors and drug metabolizing cytochrome P450 (2010)
  • Author(s): Nakajima M
  • Organizer: 9th International Society for Study of Xenobiotics Meeting
  • Place of Presentation: Istanbul Lutfi Kirdar Convention and Exhibition Center(Turkey)
  • Year and Date: 2010-09-07
• [Presentation] Human PPARa is regulated by miR-21 (2010)
  • Author(s): Kida K, Nakajima M, Mohri T, Oda Y, Takagi S, Fukami T, Yokoi T
  • Organizer: 9th International Society for Study of Xenobiotics Meeting
  • Place of Presentation: Istanbul Lutfi Kirdar Convention and Exhibition Center(Turkey)
  • Year and Date: 2010-09-07
• [Presentation] マイクロRNAによるシトクロムP450の発現調節 (2010)
  • Author(s): 中島美紀
  • Organizer: 第37回日本トキシコロジー学会学術年会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2010-06-16
• [Presentation] Human hepatocyte nuclear factor 4αis regulated bystress-induced microRNAs (2009)
  • Author(s): Takagi S, Naka. lima M, Kida K, Yamaura Y, Fukami T, Yokoi T
  • Organizer: 第24回日本薬物動態学会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-11-27
• [Presentation] Human CYP2E1 is post-transcriptionally regulated by microRNA (2009)
  • Author(s): Mohri T, Nakajima M, Fukami T, Takamiya M, Aoki Y, Yokoi T
  • Organizer: 第24回日本薬物動態学会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-11-27
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~taisha/index.html