Circulating MicroRNAs: What Is Their Relevance?

MicroRNAs (miRNAs)3 are small (approximately 22-nucleotide) RNA molecules that posttranscriptionally regulate protein-coding gene expression by binding to either fully or partially complimentary sequences within target messenger RNA (mRNA). Over 2000 unique miRNAs have been identified in humans (1) and these miRNAs can act to either fine tune or markedly alter protein expression of numerous mRNA targets simultaneously, allowing for an enormously complex layer of regulation of cellular pathways. Much interest has focused on the clinical and therapeutic potential of miRNAs, and pharmacological treatments targeting miRNAs are being developed and tested in research trials (2). miRNAs have recently been identified extracellularly in bodily fluids, and differences in peripheral miRNA profiles have been observed in several disease states (3). Furthermore, miRNAs have been found to be stable to digestion by ribonucleases (RNAases), repeated freeze–thaw cycles, and prolonged storage (3). These properties mean that extracellular miRNAs may have potential for use in diagnostic and prognostic testing and in personalizing or targeting therapies, as well as enabling identification of novel pathways and molecular mechanisms of disease.Several previous studies have examined the expression patterns of intracellular miRNAs within adipose tissue and during adipogenesis and have demonstrated their functional significance (4). In this issue of Clinical Chemistry , Ortega et al. (5) assessed circulating genomewide miRNA expression in individuals at different levels of obesity and in response to weight loss. The authors found that the expression of several miRNAs in plasma changed significantly with obesity. The authors were also able to identify a signature of miRNAs with a high specificity for morbid obesity. Interestingly, several of the same miRNAs that were regulated in obesity were also identified as changing in the circulation of individuals following weight loss induced by bariatric surgery. However, when weight loss achieved by bariatric surgery was compared with that …