Analysis on the expression of protein regulating pharmacokinetics via oxidative stress-response lncRNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Mie University
• Principal Investigator: IKEMURA Kenji 三重大学, 医学部附属病院, 薬剤師 (70513935)
• Co-Investigator(Kenkyū-buntansha): 奥田 真弘 三重大学, 医学部附属病院, 教授 (70252426)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Long-noncoding RNA / 酸化ストレス / 薬物トランスポータ / P-糖蛋白質

Outline of Final Research Achievements

Long-noncoding RNA (lncRNA) should regulate the expression of drug-metabolizing enzymes and drug transporters, which affect the efficacy and adverse effect of drugs. In the present study, we demonstrated that the expression level of P-glycoprotein (P-gp/MDR1) was increased in human colon carcinoma cell line Caco-2 cell by the exposure of oxidative stress. In addition, the present findings suggested that CRNDE (Colorectal neoplasia differentially expressed), which is a type of lncRNA, regulated the expression of MDR1.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

lncRNAは、年齢・性別・疾患により発現量が変動することから、これまで未解決であった薬の薬効や副作用発現の個人差の解明に寄与する可能性が高く、今後の更なる研究の発展が期待される。また、P-糖蛋白質はがん細胞における抗がん薬耐性化に密接に関わる分子であることから、P-糖蛋白質の新たな発現調節機構の解明により、抗がん薬の耐性化の克服や抗がん薬の安全かつ有効な薬物治療の実現にも貢献可能である。