Analysis of miRNA as a novel biomarker for estimating transporter's function in the human organs

• Project/Area Number: 15K15004
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: Ieiri Ichiro 九州大学, 薬学研究院, 教授 (60253473)
• Co-Investigator(Kenkyū-buntansha): 廣田 豪 九州大学, 薬学研究院, 准教授 (80423573)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 薬剤反応性 / miRNA / 生体試料中濃度 / トランスポーター / 薬物トランスポーター / 薬物代謝酵素

Outline of Final Research Achievements

In this study, we analyzed Breast Cancer Resistance Protein (BCRP) and Organic Anion Transporting Polypeptide 1B1（OATP1B1）for evaluating miRNA expression as a biomarker to predict the activities in the drug transporters.
A variant in the breast cancer resistance protein (BCRP) gene, 421C>A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Our study showed that intestine-derived exosomal miR-328 levels positively correlated with SASP AUC0-48. OATP1B1, which is expressed specifically in human liver, mediates the various drugs, such as bile acid and statins. We identified one miRNA which was negatively correlated with OATP1B1 mRNA levels. Our results suggest that miRNA is a novel biomarker for estimating transporter’s function in the human organs.

Research Products

• [Journal Article] Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines (2016)
  • Author(s): Gotanda K, Hirota T, Saito J, Fukae M, Egashira Y, Izumi N, Deguchi M, Kimura M, Matsuki S, Irie S, Ieiri I
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 32299-32299
  • DOI: 10.1038/srep32299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ABCG2遺伝子376C>T変異がスルファサラジンの体内動態に与える影響 (2016)
  • Author(s): 廣田豪、五反田圭介、徳本知子、深江真登、家入一郎
  • Organizer: 日本薬物動態学会 第31回年会
  • Place of Presentation: 長野県松本市
  • Year and Date: 2016-10-13