MicroRNA Polymorphisms

Prasun J Mishra, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA
Rita Humeniuk, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA

Published online: April 2013

DOI: 10.1002/9780470015902.a0022428

MicroRNAs (miRNAs) are evolutionarily conserved small noncoding ribonucleic acids (RNAs). Owing to their ability to orchestrate a vast majority of tissue-specific genes in a cell, miRNAs are referred to as microsheriffs or the micromanagers of gene expression. Accumulating evidence now suggests that genetic variation or polymorphisms present in the miRNA pathway are associated with the prognosis and progression of diseases and drug responses and are emerging as powerful tools to study the biology of diseases. MicroRNA polymorphisms (miR-polymorphisms) can be defined as polymorphisms (SNPs, chromosomal changes, epigenetic defects, mutations, alterations and variations) that may potentially interfere with miRNA-mediated regulation of cellular functions and can be present not only in the miRNA target gene but also in pri-, pre-, mature-miRNA sequences, in the genes involved in miRNA biogenesis and in miRNA cis-regulatory elements (e.g. promoter). A polymorphism in mature miRNAs may affect expression of several genes and have serious consequences, whereas a polymorphism in miRNA target site may be more target and/or pathway specific. The discovery of the role of miRNA in drug resistance and miR-polymorphisms to predict drug response has led to the development of a new field in biomedical science called miRNA pharmacogenomics, a study of the miRNAs and miR-polymorphisms affecting expressions of drug target genes, to predict drug behaviour and to improve drug efficacy. Detection of miRNA-polymorphisms can potentially improve diagnosis, treatment and prognosis in patients and has profound implications in the fields of pharmacogenomics and personalised medicine.

Key Concepts:

  • miRNAs can potentially orchestrate expression of multiple genes and pathways.
  • miRNA-polymorphisms/-variations/-SNPs/-mutations can interfere with miRNA function and affect gene expression and its detection holds promise in the field of miRNA pharmacogenomics, molecular epidemiology and for individualised medicine.
  • In a population, miR-polymorphisms can be present either in a heterozygous or homozygous configuration, in the form of insertions, deletions, amplifications or chromosomal translocations, resulting in loss or gain of a miRNA site/function.
  • A cell with a variant miRNA may be naturally selected. For example, a variation that gives rise to high levels of an oncogenic miRNA will be favourably selected in cancer cells to impart a growth advantage.
  • miR-polymorphisms can be classified into several categories affecting various steps of miRNA biogenesis, that is, transcription, processing, targeting and can be present not only in the miRNA target gene but also in the genes involved in miRNA biogenesis and in pri-, pre- and mature-miRNA sequences.
  • A polymorphism in a processed miRNA may affect expression of several genes and have serious consequences, whereas a polymorphism in a miRNA target site, in target mRNA, may be more target and/or pathway specific.
  • miRNAs and miR-polymorphisms could be potential predictors of drug response in the clinic and may provide more accurate methods of determining appropriate drug dosages based on a patient's genetic makeup.
  • miR-polymorphisms are associated with progression and prognosis of diseases such as cancer, neurological disorders, muscular hypertrophy, gastric mucosal atrophy, cardiovascular disease and Type II diabetes, etc.
  • miRNAs and miR-polymorphisms are powerful tools to study disease progression and can be used in the clinic to predict drug response (or efficacy).

Keywords: microRNA polymorphisms; genetic variations; mutations; drug resistance; disease; diagnosis; prognosis; classification; individualised medicine; personalised medicine; genome medicine; epidemiology; epigenetics; miRSNP; pharmacogenomics

Figure 1. miRNA polymorphisms are associated with disease progression and can be used to predict drug resistance/drug response.
Figure 2. miRNA biogenesis and function; miRNA polymorphisms can affect various steps involved in miRNA biogenesis and function. Adapted with permission from Mishra and Bertino (2009) © Future Medicine Ltd.
Figure 3. miRNA polymorphisms affecting miRNA function and their classification. Adapted with permission from Mishra and Bertino (2009) © Future Medicine Ltd.
Figure 4. A model describing the mechanism of action of a miR-polymorphism by using drug response as an example. Adapted with permission from Mishra and Bertino (2009) © Future Medicine Ltd.
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Related Sub-Topics:

Pharmacogenetics and Pharmacogenomics | Inter-Individual Variation and Polymorphism | Epigenetics and Disease | Translational Regulation | RNA Structure and Function
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Article Title: MicroRNA Polymorphisms
 
How to Cite close
Mishra, Prasun J, and Humeniuk, Rita(Apr 2013) MicroRNA Polymorphisms. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022428]