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.

Could MicroRNA polymorphisms influence warfarin dosing? A pharmacogenetics study on mir133 genes

“…It is evident that miRNAs could control also the expression of genes that are involved in drug response and therefore they could also play a role in Pharmacogenomics. Several studies have described the role of miRNA in drug response especially in cancer treatments in terms of drug resistance [18][19][20] but also in inflammatory bowel disease treatment [21]. Few studies have also described that polymorphisms in miRNA target regions could affect the expression of the genes and therefore the response to the treatment.…”

“…MicroRNAs (miRNAs or miRs) are a recently discovered class of small (19)(20)(21)(22)(23)(24) nucleotides) endogenous non-coding oligonucleotides that regulate gene expression at the post-transcriptional level [1][2][3]. They play a crucial role in regulation of physiological and pathological processes and some miRNAs have been described as associated with distinct clinical characteristics, such as diagnosis or disease activity [4][5][6][7][8][9].…”

Glucocorticoid inhibits cell proliferation in differentiating osteoblasts by microRNA-199a targeting of WNT signaling

“…( De Iudicibus et al 2013). In the present study, we did not explore whether GR was involved in the regulation of miR199a-5p by GCs in osteoblasts.…”

“…Results described in several recent reports have indicated that GCs exert post-transcriptional control through the regulation of miRNA processing and expression (De Iudicibus et al 2013). Xing et al (2014) reported that GCs induced apoptosis by inhibiting miRNA cluster miR-17-92 expression in chondrocytic cells.…”

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

“…Specifically, they found that MiR-31 expression levels increased with disease progression and accurately discriminated neoplastic from normal or chronically inflamed tissues in IBD patients. miRNAs might also be used as tools in predicting or assessing response to therapy, as miRNA levels before and after glucocorticoid (GC) treatment appeared to be significantly different [159]. In addition, when serum samples of 19 patients receiving IFX induction therapy were analyzed, miRNA levels of let-7d and let-7e were significantly increased in the clinical remission group [160].…”