microRNA and internal medicine: from pathophysiology to the new diagnostic and therapeutic procedures

Česká verzia

Authors: Jan Novák ^1,2; Miroslav Souček ¹
Authors place of work: II. interní klinika LF MU a FN U sv. Anny v Brně ¹; Fyziologický ústav LF MU v Brně ²
Published in the journal: Vnitř Lék 2016; 62(6): 477-485
Category: Reviews

Summary

microRNAs (abbreviated miRNAs or miRs) represents one of the group of so called small non-coding RNAs which participate in the negative post-transcriptional regulation of gene expression. According to the base complementarity they target molecules of messenger RNAs (mRNAs) which results either in translational blockade or in degradation of target mRNA. One miRNA usually targets more mRNA and one mRNA is usually targeted by more than one miRNA – complicated and interconnected regulatory networks are thus created and their disruption leads to the abnormalities in development or results in the development of diseases. Within the past two decades, novel mechanisms were described that enable us to modulate miRNA levels (either causing upregulation or downregulation) – miRNAs can thus be considered as a novel potential group of therapeutic targets. First clinical trials using the blockade of liver specific miR-122 showed very promising results in the treatment of chronic hepatitis C virus infection. Results of preclinical and animal studies are also promising providing future rationale for the development of new therapeutics for various internal diseases including heart failure, bronchial asthma or inflammatory bowel diseases. Moreover, miRNAs are not only affecting the pathophysiology of internal diseases, but they can also reflect their presence – there is a group of miRNAs called extracellular, or circulating miRNAs, i.e. miRNAs that are present in extracellular space including all known body fluids such as plasma, serum, urine, saliva or sweat. Circulating miRNAs are stable; their levels are constant among the individuals of one species, methods determining their levels are reproducible and last but not least – levels of extracellular miRNAs differ between healthy and diseased individuals. They are released into the circulation either after the cell necrosis or by active transport. Except of being potential novel biomarkers, these miRNAs represent a novel mean of intercellular communication. Their levels thus reflect not only the organ damage but also the changes of the homeostasis during various illnesses. The aim of the current study is to provide the first insight into the miRNA world to clinicians, especially to internal medicine specialists. Using simple examples from clinical praxis or clinical pathophysiology, we are trying to present diagnostic and therapeutic potential that is hidden within these tiny interesting molecules.

Key words:
circulating microRNA – diagnostics – internal diseases – microRNA – therapy

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