Current knowledge of microRNA-mediated regulation of drug metabolism in humans
Current knowledge of microRNA-mediated regulation of drug metabolism in humans
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DOI：
10.1080/17425255.2018.1472237
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发表时间：
2018-05
影响因子：
4.3
通讯作者：
Masataka Nakano;M. Nakajima
中科院分区：
文献类型：
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作者：
Masataka Nakano;M. Nakajima
摘要 简介：了解导致个体间和个体内药物代谢效力差异的因素是个性化或精准医疗实践以及促进高效药物开发的必要条件。药物代谢酶的表达受到核受体和转录因子的转录调控、表观遗传调控（例如 DNA 甲基化和组蛋白乙酰化）以及翻译后修饰的控制。除了此类调节机制之外，最近的研究还表明，microRNA (miRNA) 是一种内源性~22 核苷酸非编码 RNA，通过 mRNA 的翻译抑制和降解来调节基因表达，对药物代谢酶的转录后调节有显着贡献。涵盖领域：本综述总结了目前有关药物代谢酶和转录因子的 miRNA 依赖性调节及其生理和临床意义的知识。我们还描述了 miRNA 依赖性调控研究的最新进展，表明假基因、单核苷酸多态性和 RNA 编辑的存在会影响 miRNA 靶向。专家观点： miRNA是导致个体间和个体内药物代谢酶表达差异的关键因素，这是不容动摇的事实。考虑 miRNA 依赖性调控将是优化个性化和精准医疗的有用工具。
ABSTRACT Introduction: Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.