Micro RNA-mediated expressional regulation of transporters

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15158
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: Ikumi Tamai 金沢大学, 薬学系, 教授 (20155237)
• Co-Investigator(Kenkyū-buntansha): 中西 猛夫 金沢大学, 薬学系, 准教授 (30541742) ; 中島 美紀 金沢大学, 薬学系, 教授 (70266162)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: トランスポーター / OATP / マイクロRNA / ナノ粒子 / 薬食相互作用 / 薬物間相互作用 / 個体間変動

Outline of Final Research Achievements

To understand the mechanisms for altered drug absorption and disposition by co-administered drugs and foods, we studied possible involvement of micro RNA (miRNA) on the expressional regulation of drug transporter OATPs. (1) OTAP2B1, which is expressed both in liver and intestine, was found to be regulated by specific miRNA by in vitro experiments. (2) Statins are very good substrates of OATPs and they have possibility to cause myopathy as side effect. We succeeded to suggest several miRNA that can be used for diagnosis of myopathy. (3) As the mechanism of drug-food interaction, it was demonstrated that apple-derived nanoparticles include many miRNAs and they affect expression of OATP2B1, suggesting that food-derived miRNAs could regulate expression of OATPs, (4) Transporters responsible for intestinal absorption of anti-cancer nucleoside analogue were identified and further studies to demonstrate the mechanisms to regulate their expression, including miRNA should be conducted.

Free Research Field

薬物動態学