Integrative approaches for studying the role of noncoding RNAs in influencing drug efficacy and toxicity

Abstract

Introduction Drug efficacy and toxicity are important factors for evaluation in drug development. Drug metabolizing enzymes and transporters (DMETs) play an essential role in drug efficacy and toxicity. Noncoding RNAs (ncRNAs) have been implicated to influence inter-individual variations in drug efficacy and safety by regulating DMETs. An efficient strategy is urgently needed to identify and functionally characterize ncRNAs that mediate drug efficacy and toxicity through regulating DMETs. Areas covered : We outline an integrative strategy to identify ncRNAs that modulate DMETs. We include reliable tools and databases for computational prediction of ncRNA targets with regards to their advantages and limitations. Various biochemical, molecular, and cellular assays are discussed for in vitro experimental verification of the regulatory function of ncRNAs. In vivo approaches for association of ncRNAs with drug treatment and toxicity are also reviewed. Expert opinion : A streamlined integration of computational prediction and wet-lab validation is important to elucidate mechanisms of ncRNAs in the regulation of DMETs related to drug efficacy and safety. Bioinformatic analyses using open-access tools and databases serve as a powerful booster for ncRNA research in toxicology. Further refinement of computational algorithms and experimental technologies is needed to improve accuracy and efficiency in ncRNA target identification and characterization.