微小RNA作为药物基因组生物标志物用于药物疗效和药物安全性评估。
microRNAs as pharmacogenomic biomarkers for drug efficacy and drug safety assessment.
作者信息
Koturbash Igor, Tolleson William H, Guo Lei, Yu Dianke, Chen Si, Hong Huixiao, Mattes William, Ning Baitang
机构信息
Department of Environmental & Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
National Center for Toxicological Research, US Food & Drug Administration, Jefferson, AR 72079, USA.
出版信息
Biomark Med. 2015;9(11):1153-76. doi: 10.2217/bmm.15.89. Epub 2015 Oct 26.
Abstract
Much evidence has documented that microRNAs (miRNAs) play an important role in the modulation of interindividual variability in the production of drug metabolizing enzymes and transporters (DMETs) and nuclear receptors (NRs) through multidirectional interactions involving environmental stimuli/stressors, the expression of miRNA molecules and genetic polymorphisms. MiRNA expression has been reported to be affected by drugs and miRNAs themselves may affect drug metabolism and toxicity. In cancer research, miRNA biomarkers have been identified to mediate intrinsic and acquired resistance to cancer therapies. In drug safety assessment, miRNAs have been found associated with cardiotoxicity, hepatotoxicity and nephrotoxicity. This review article summarizes published studies to show that miRNAs can serve as early biomarkers for the evaluation of drug efficacy and drug safety.
摘要
大量证据表明，微小RNA（miRNA）通过涉及环境刺激/应激源、miRNA分子表达和基因多态性的多向相互作用，在调节药物代谢酶和转运体（DMET）以及核受体（NR）产生的个体间差异中发挥重要作用。据报道，miRNA表达受药物影响，而miRNA本身可能影响药物代谢和毒性。在癌症研究中，已鉴定出miRNA生物标志物可介导对癌症治疗的内在和获得性耐药性。在药物安全性评估中，已发现miRNA与心脏毒性、肝毒性和肾毒性有关。这篇综述文章总结了已发表的研究，以表明miRNA可作为评估药物疗效和药物安全性的早期生物标志物。
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