MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel diseases

Abstract

In spite of the introduction in therapy of highly effective biological agents, glucocorticoids (GCs) are still employed to induce remission in moderate to severe inflammatory bowel diseases (IBD), but considerable inter-individual differences in their efficacy and side effects have been reported. The effectiveness of these drugs is indeed very variable and side effects, particularly severe in pediatric patients, are common and often unpredictable: the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability. In this context, microRNAs (miRNAs) represent a new and promising field of research. miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level, and are fine-tuning regulators of diverse biological processes, including the development and function of the immune system, apoptosis, metabolism and inflammation. Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases, such as IBD. There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response; however, the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study. The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis, represents an important innovative approach that could be translated into clinical practice. In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs, and their potential role as molecular markers useful for predicting in advance GC response.

Keywords: Glucocorticoids; Inflammatory bowel diseases; MicroRNA; Molecular markers; Pharmacogenomics

Core tip: Studies on microRNAs (miRNAs) and pharmacogenomics represent a promising investigation topic that could increase the understanding of the pharmacology of steroids in inflammatory bowel diseases (IBDs) and possibly in other diseases. A number of studies have shown that glucocorticoids (GCs) can modify the expression profiles of different miRNAs, however, the obtained results have been highly variable, and to date it is not possible to recognize a specific miRNA pattern regulated by GCs. Moreover, existing studies employed techniques based on the use of reverse transcription quantitative polymerase chain reaction and microarrays, through the analysis and quantification of already known miRNAs. Using next generation sequencing technologies, it could be possible to detect novel, still unrecognised miRNAs, and identify new miRNA isoforms (iso-miRs) as well. This innovative approach could be a valuable tool for a better understanding of the role of miRNAs to predict steroid response in IBDs. In the future, the increased availability and the reduced costs of RNA profiling should enable the clinicians to stratify patients on specific miRNA biomarkers before starting GC treatment.