Mishra Prasun J, Bertino Joseph R
Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD 20892-4264, USA.
Pharmacogenomics. 2009 Mar;10(3):399-416. doi: 10.2217/14622416.10.3.399.
Referred to as the micromanagers of gene expression, microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs. Polymorphisms in the miRNA pathway (miR-polymorphisms) are emerging as powerful tools to study the biology of a disease and have the potential to be used in disease prognosis and diagnosis. Detection of miR-polymorphisms holds promise in the field of miRNA pharmacogenomics, molecular epidemiology and for individualized medicine. MiRNA pharmacogenomics can be defined as the study of miRNAs and polymorphisms affecting miRNA function in order to predict drug behavior and to improve drug efficacy. Advancements in the miRNA field indicate the clear involvement of miRNAs and genetic variations within the miRNA pathway in the progression and prognosis of diseases such as cancer, neurological disorders, muscular hypertrophy, gastric mucosal atrophy, cardiovascular disease and Type II diabetes. Various algorithms are available to predict miRNA-target mRNA sites; however, it is advisable to use multiple algorithms to confirm the predictions. Polymorphisms that may potentially affect miRNA-mediated regulation of the cell can be present not only in the 3 -UTR of a miRNA target gene, but also in the genes involved in miRNA biogenesis and in pri-, pre- and mature-miRNA sequences. A polymorphism in processed miRNAs may affect expression of several genes and have serious consequences, whereas a polymorphism in miRNA target site, in the 3 -UTR of the target mRNA, may be more target and/or pathway specific. In this review, we for the first time suggest a classification of miRNA polymorphisms/mutations. We also describe the importance and implications of miR-polymorphisms in gene regulation, disease progression, pharmacogenomics and molecular epidemiology.
微小RNA（miRNA）被称为基因表达的微观管理者，是进化上保守的小型非编码RNA。miRNA途径中的多态性（miR-多态性）正成为研究疾病生物学的有力工具，并有可能用于疾病的预后和诊断。miR-多态性的检测在miRNA药物基因组学、分子流行病学和个性化医学领域具有广阔前景。miRNA药物基因组学可定义为对miRNA及其影响miRNA功能的多态性进行研究，以预测药物行为并提高药物疗效。miRNA领域的进展表明，miRNA及其途径内的基因变异明显参与了癌症、神经疾病、肌肉肥大、胃黏膜萎缩、心血管疾病和II型糖尿病等疾病的进展和预后。有多种算法可用于预测miRNA靶向mRNA的位点；然而，建议使用多种算法来确认预测结果。可能潜在影响miRNA介导的细胞调控的多态性不仅可能存在于miRNA靶基因的3'-UTR中，还可能存在于参与miRNA生物合成的基因以及初级、前体和成熟miRNA序列中。加工后的miRNA中的多态性可能会影响多个基因的表达并产生严重后果，而靶mRNA的3'-UTR中miRNA靶位点的多态性可能更具靶点和/或途径特异性。在本综述中，我们首次提出了miRNA多态性/突变的分类。我们还描述了miR-多态性在基因调控、疾病进展、药物基因组学和分子流行病学中的重要性及意义。
