MicroRNAs: powerful regulators and potential diagnostic tools in cardiovascular disease

Their power as regulators is demonstrated by the fact that up to 30-50% of genes are controlled by miRNAs [4].The most recent version of the central miRNAs database (v21.0),available at the website miRBase.org,contains 35,828 mature miRNA products, in 223 species.To date, there have been 1,881 precursors and 2,588 mature miRNAs annotated and described in humans [5].MiRNAs are initially transcribed from nuclear DNA to long primary transcripts (pri-miRs) by the RNA-polymerase II, and the majority of them are subsequently spliced by the Drosha RNase III-cofactors complex.Transported out of the nucleus by exportin-5, pre-miRs are cleaved by Dicer RNA-processing ribonuclease III into small double stranded miR-miR* duplexes (Fig. 1).The mature (functional) miR strand is loaded into the RNA-induced silencing complex, where it can guide the mRNA silencing by either degradation or translational inhibition, whereas the complementary passenger strand miR is degraded or incorporated into small vesicles called exosomes and released from the cell.Both pre-miRNA and mature miRNA present in cytoplasm can be released from the cell in microvesicles.MiRNAs circulate in the blood in association with RNA-binding proteins argonaute2 (Ago2) or high-density lipoproteins.The transport out of the cell may be conducted passively in apoptotic bodies, or actively through the channel proteins [6].Released miRNAs can then act as intercellular communicators and influence gene expression in the target cells [7].The function of miRNA has been most thoroughly investigated to date in the field of oncology.By regulating differentiation in both normal and cancer cells, miRNAs can act as tumour oncogenes or tumour suppressors [8].Their role in the development of several types of human neoplasms has been identified [9].For instance, polymorphism in miR-146a is a predisposing factor for thyroid carcinogenesis [10,11].As a consequence, miRNAs are emerging as new prognostic