CHAPTER 3: Circulating MicroRNAs as Biomarkers of Celiac Disease and Other Intestinal Pediatric Diseases: Experimental and Bioinformatics Challenges From Bench to Bedside

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at post-transcriptional level and play a key role in the pathogenesis of gastrointestinal and other pediatric diseases. Previous studies have revealed that miRNAs are dysregulated in intestinal biopsies of patients affected by intestinal diseases. These miRNAs belong to several important biological processes, such as Wnt signaling, cell proliferation and differentiation and adherens junction pathways. miRNAs are also present in extracellular spaces, packaged into various membrane-bound vesicles or associated with RNA-binding proteins. Circulating miRNAs are highly stable and can act as intercellular messengers, affecting many physiological processes. miRNAs circulating in body fluids have generated a strong interest as potential use as clinical biomarkers. In fact, their remarkable stability and the relative ease of detection make circulating miRNAs ideal tools for rapid and non-invasive diagnosis. Therefore, we have outlined recent insights about the origin, functions and diagnostic potential of extracellular miRNAs by focusing on the feasibility of using different sampling sources for the development of non-invasive pediatric diagnostics. We will also discuss specific bioinformatics tools and databases for circulating miRNAs used for the identification and discovery of novel diagnostic biomarkers and for investigating the functional role of miRNAs in intestinal and other pediatric diseases.