Epigenetics and doping in sports—The role of microRNAs

Epigenetic markers have been extensively employed to identify several physiological and/or pathological conditions, as they are associated with a long list of biological processes, including DNA methylation, histone modifications, genomic imprinting, and regulation of protein-coding mRNAs mediated by microRNAs (miRNAs). miRNAs are small noncoding RNAs (15–25 nucleotides in length) able to bind the 3′UTR and, less frequently, 5′UTR and coding sequences (CDS) of target mRNAs leading to mRNA-translation repression and/or mRNA degradation, depending on binding affinity. Recently, miRNAs have been extensively investigated as epigenetic biomarkers for the identification of physiological alterations, such as doping-related procedures, thanks to their easily detection and stability in a large variety of body fluids including bloods and derivatives (plasma and serum). As for several physiological alterations, it is expected that the miRNA expression profile may be altered following the exposure to agents employed in doping procedures. In agreement with this hypothesis circulating miRNAs were found to be associated with administration of human testosterone and growth-hormone and have been proposed as long-term biomarkers for the detection of the erythropoiesis-stimulating agent CERA. Hypoxia-regulated miRNAs might be used to identify the HIF Stabilizer Molidustat. In addition, despite the occurrence of possible confounding factors (changes in the miRNA expression profile during blood storage, aging, exercise, environment), miRNAs have been proposed as potential markers of autologous blood transfusion in sports.