microRNA对药物体内过程调控的研究进展

The research progress of microRNA on regulation of drug disposition in vivo

药物的体内过程需经一系列的生物转化和转运途径,依赖于药物代谢酶和转运体的参与。而个体对同一药物的代谢、转运能力存在差异,这一差异不能完全用药物基因组学解释。microRNA作为表观遗传修饰的一个重要方面,是对传统遗传学的强有力补充。人体内多种药物代谢酶和转运体均受到不同的microRNA调控,同一microRNA又可同时调控不同的代谢酶或(和)转运体,二者均提示microRNA极有可能实现较为广泛的宏观调控。该文分别从microRNA对药物代谢酶的调控、对药物转运体的调控以及同时调控代谢酶及转运体的microRNA三个方向综合分析,为研究药物个体差异提出一个极好的切入点,并为合理用药和个体化医疗提供理论基础。

The disposition of drug in vivo is subjected to a series of biotransformation and transport,depending on the involvement of drug-metabolizing enzymes and transporters. However,the individual capacity varies when metabolizing and transporting the same drug,and pharmacogenomics has trouble in completely explaining the differences. microRNA,a key aspect of epigenetic modifications,is a powerful complement to traditional genetics.Emerging evidences have confirmed that drug-metabolizing enzymes and transporters be controlled by different microRNAs,and the same microRNA also regulates several drug-metabolizing enzymes or/and transporters simultaneously. All of these researches infer that microRNAs are likely to realize the comprehensive macro-regulation of gene expression. The further study of microRNAs maybe a suitable point to research the interindividual variability in disposition of drugs,and it provides a theoretical basis for rational use of drug and individualized medicine.