Newer Insights in Personalized and Evidence Based Medicine- the Role of MicroRNAs

Background: MicroRNAs are non-coding RNAs which regulate gene expression by binding to 3’ UTR site on mRNA. These small RNAs repress gene expression by interfering with the process of translation or by degrading the target mRNA. Abnormal expression of miRNAs has been implicated in a wide spectrum of human diseases like atherosclerosis, cancers and diabetes. Traditionally, pharmacogenomics focuses on single nucleotide polymorphisms and copy number variants of genes implicated in pharmacokinetics and pharmacodynamics. Recently, drug response has been proposed to be regulated by microRNAs. Mutations involving miRNAs can contribute to disease pathogenesis and modulation of drug response. Objective: The main objective of this review is to highlight the role of miRNAs in biological processes leading to disease states as well as in the field of drug action and pharmacogenomics. Method: A literature review was performed incorporating the latest insights in the field of miRNA therapeutics, diagnostics and pharmacogenomics. Results: Altered expression of miRNAs is seen in diabetes, vascular inflammation, atherosclerosis, infection and cancers. In the field of miRNA- pharmacogenomics, maximum work has been done studying the resistance to anticancer drugs. Some examples of microRNAs regulating drug response are miR-24 influencing the response to methotrexate, miR-125b affecting the action of calcitriol and miR-27b regulating the expression of CYP3A4. Among miRNAs currently being targeted in therapeutics are miR-122, miR- 33, miR-21, let-7 and miR-34. Conclusion: A significant fraction of all mRNAs transcribed in a cell are regulated by miRNAs. miRNAs implicated in a given disease may interfere with drug action and metabolism. Further research is needed to understand the association between miRNA, mRNAs, diseases and pharmacokinetics and dynamics.