Circulating miRNAs as sensitive and specific biomarkers for the diagnosis and monitoring of human diseases: Promises and challenges

Abstract The regulation and modulation of gene expression has been a central focus of modern biomedical research ever since the first molecular elucidation of DNA. The cellular mechanisms by which genes are expressed and repressed hold valuable insight for maintaining tissue homeostasis or conversely provide mechanistic understanding of disease progression. Hence, the discovery of the first miRNA in humans roughly a decade ago profoundly shook the previously established dogmas of gene regulation. Since, these small RNAs of around 20 nucleotides have unquestionably influenced almost every area of medical research. This momentum has now spread to the clinical arena. Hundreds of papers have already been published shedding light on the mechanisms of action of miRNAs, their profound stability in almost every bodily fluid and relating their presence to disease state and severity of disease progression. In this review, we explore the diagnostic potential of miRNAs in the clinical laboratory with a focus on studies reporting the detection of miRNAs in blood and urine for investigation of human disease. Sensitivities, specificities, areas under the curve, group descriptions and miRNAs of interest for 69 studies covering a broad range of diseases are provided. We discuss the practicality of miRNAs in the screening, diagnosis and prognosis of a range of pathologies. Characteristics and pitfalls of miRNA detection in blood are also discussed. The topics covered here are pertinent in the design of future miRNA-based detection strategies for use in clinical biochemistry laboratory settings.