Regulation of drug transporters by microRNA and implications in disease treatment

Background: Transporters play crucial roles in the pharmacokinetics of drugs, consequently influencing efficacy and toxicity by unexpectedly altering drug concentrations. Epigenetic regulation by microRNAs (miRNAs) is a critical determinant of transporter function. Several miRNAs have been reported to regulate transporter expression via direct or indirect pathways, resulting in altered pharmacokinetics and drug responses. Area covered: In this review, we provide an overview of the regulatory mechanisms of transporters, particularly with regard to clinically important transporters, via miRNAs and also summarize the associations between miRNAs and transporter expression. We also present clinical implications for miRNA-dependent alterations in transporter expression to highlight the importance of miRNAs in pharmacokinetics and drug responses. Expert opinion: Available information on the implications of miRNAs in drug transporter have been mainly reported in cancers for ATP binding cassette (ABC) transporters. Although solute carrier (SLC) transporters are essential for drug pharmacokinetics, information on the regulatory mechanisms of SLC transporters by miRNAs is still limited compared with ABC transporters. Additional information on the pharmacokinetic implications of the interplay between miRNAs and transporters is necessary for improving drug therapies; thus, investigations of the miRNA-dependent regulatory mechanisms of transporters and their implications need to be expanded to provide insights into safe and effective drug regimens.