Post-transcriptional regulation of CYP3A4 by miRNA

• Project/Area Number: 19790121
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: NAKAJIMA Miki Kanazawa University, 薬学系, 准教授 (70266162)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 薬物代謝 / シトクロムP450 / 発現調節 / マイクロRNA / 核内レセプター / 薬物代謝酵素 / 転写因子

Research Abstract

主要な薬物代謝酵素であるヒトCYP3A4の発現量や酵素活性に認められる大きな個人差の原因を明らかにすることを目的として、その発現制御にmicroRNAが関与している可能性を検討した。その結果、核内レセプターであるpregnane X receptorがmiR-148aによって転写後調節されており、それが原因でCYP3A4発現量の個人差が生じていることを明らかにした。遺伝子多型や転写調節など従来の概念では説明できなかった現象を解明することができた

Research Products

• [Journal Article] Post-transcriptional regulation of human pregnane X receptor by microRNA affects the expression of cytochrome P450 3A4. J. (2008)
  • Author(s): Shingo Takagi, Miki Nakajima, Takuya Mohri, and Tsuyoshi Yokoi.
  • Journal Title: Biol. Chem. 283 Pages: 9674-9680
  • Peer Reviewed
• [Journal Article] Post-transcriptional regulation of human pregnane X receptor by microRNA affects the expression of cytochrome P450 3A4 (2008)
  • Author(s): Shingo Takagi, Miki Nakajima, Takuya Mohri, Tsuyoshi Yokoi
  • Journal Title: Journal of Biological Chemistry 283(15) Pages: 9674-9680
  • Peer Reviewed
• [Presentation] 薬物代謝酵素と核内レセプターのmicroRNAによる発現制御 (2008)
  • Author(s): 中島美紀、高木信伍、駒形小夜香、茂利拓也、土屋佑樹、横井毅
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本
• [Presentation] CYP enzymes and cancer: regulation by steroids and miRNA. (2008)
  • Author(s): Tsuyoshi Yokoi and Miki Nakajima
  • Organizer: 9th Advanced Course on Steroid Enzymes and Cancer
  • Place of Presentation: Erice, Italy
• [Presentation] CYP enzymes and cancer : regulation by steroids and miRNA (2008)
  • Author(s): Tsuyoshi Yokoi and Miki Nakaiima
  • Organizer: 9th Advanced Course on Steroid Enzymes and Cancer
  • Place of Presentation: Erice, Italy
• [Presentation] miR-148aによるヒトpregnane X receptor (PXR)の発現制御とCYP3A4の発現に及ぼす影響 (2007)
  • Author(s): 高木信伍、中島美紀、茂利拓也、加藤美紀、横井毅
  • Organizer: 第17回アンチセンスシンポジウム
  • Place of Presentation: 金沢
• [Presentation] ヒトPXRのmicroRNAによる転写後調節 (2007)
  • Author(s): 高木信伍、中島美紀、茂利拓也、横井毅
  • Organizer: 第5回ながの遺伝子発現調節研究会
  • Place of Presentation: 上諏訪
• [Presentation] MicroRNA post-transcriptionally regulates human PXR affecting the expression level of CYP3A4 (2007)
  • Author(s): Shingo Takagi, Miki Nakajima, Takuya Mohri, Miki Katoh, and Tsuyoshi Yokoi
  • Organizer: 8th International ISSX Meeting
  • Place of Presentation: Sendai
• [Presentation] MicroRNA post-transcriptionally regulates human PXR affecting the expression level of CYP3A4 (2007)
  • Author(s): Shingo Takagi, Miki Nakajima, Takuya Mohri, Miki Katoh, Tsuyoshi Yokoi.
  • Organizer: 8th International ISSX Meeting
  • Place of Presentation: Sendai, Japan