MicroRNAs (miRs) are small, noncoding RNAs (21-25 nucleotides in size) that posttranscriptionally control gene expression by inhibiting protein translation or inducing target mRNA destabilization. Besides their intracellular function, recent studies demonstrate that miRs can be exported or released by cells and circulate with the blood in a remarkably stable form. The discovery of circulating miRs opens up intriguing possibilities to use the circulating miR patterns as biomarker for cardiovascular diseases.
Cardiac injury as it occurs after acute myocardial infarction increases the circulating levels of several myocardial-derived miRs (eg, miR-1, miR-133, miR-499, miR-208).
Talking about miR-499 scientists used array analysis of miR production in various human tissues to identify heart-specific miRs. They assessed the plasma concentrations of miR-499 in 14 individuals with acute coronary syndromes, 15 individuals with congestive heart failure, and 10 individuals without cardiovascular diseases. Plasma miR-499 concentrations were measured with a real-time reverse-transcription PCR method that used an artificial small RNA as an internal calibrator. The miRNA array analysis of various human tissues indicated that miR-499 was produced almost exclusively in the heart. Plasma miR-499 concentrations were measurably increased in all individuals with acute myocardial infarction but were below the limit of detection for all individuals in the other patient groups. So it is obvious that plasma concentration of miR-499 may be a useful biomarker of myocardial infarction in humans.
Also patients with coronary artery disease or diabetes showed reduced levels of endothelial-enriched miRs, such as miR-126. Over-expression of miR126 in a lung cancer cell line resulted in a decrease in Crk protein without any alteration in the associated mRNA. Crk is a member of a family of adaptor proteins that are involved in intracellular signal pathways altering cell adhesion, proliferation, and migration. Increased expression of Crk has been described in lung cancer and associated with increased tumor invasiveness. MiR126 overexpressed lung cancer cells exhibit a decrease in adhesion, migration, and invasion. Decreased cancer cell invasion was also evident following targeted knockdown of Crk. MiR-126 alters lung cancer cell phenotype by inhibiting adhesion, migration, and invasion and the effects on invasion may be partially mediated through Crk regulation.
These are only few examples for the potency of miRs, but undoubtedly these small molecules in the future will be not only biomarker but also potent drug.
Source: Innovita Research Foundation.