TY - JOUR T1 - High-Throughput Sequencing of microRNAs in Glucocorticoid Sensitive Paediatric Inflammatory Bowel Disease Patients. JF - Int J Mol Sci Y1 - 2018 A1 - De Iudicibus, Sara A1 - Lucafò, Marianna A1 - Vitulo, Nicola A1 - Martelossi, Stefano A1 - Zimbello, Rosanna A1 - De Pascale, Fabio A1 - Forcato, Claudio A1 - Naviglio, Samuele A1 - Di Silvestre, Alessia A1 - Gerdol, Marco A1 - Stocco, Gabriele A1 - Valle, Giorgio A1 - Ventura, Alessandro A1 - Bramuzzo, Matteo A1 - Decorti, Giuliana KW - Adolescent KW - Biomarkers KW - Child KW - Female KW - Gene Expression Regulation KW - Glucocorticoids KW - High-Throughput Nucleotide Sequencing KW - Humans KW - Inflammatory Bowel Diseases KW - Male KW - MicroRNAs KW - Receptors, Glucocorticoid KW - Transcriptome AB -

The aim of this research was the identification of novel pharmacogenomic biomarkers for better understanding the complex gene regulation mechanisms underpinning glucocorticoid (GC) action in paediatric inflammatory bowel disease (IBD). This goal was achieved by evaluating high-throughput microRNA (miRNA) profiles during GC treatment, integrated with the assessment of expression changes in GC receptor (GR) heterocomplex genes. Furthermore, we tested the hypothesis that differentially expressed miRNAs could be directly regulated by GCs through investigating the presence of GC responsive elements (GREs) in their gene promoters. Ten IBD paediatric patients responding to GCs were enrolled. Peripheral blood was obtained at diagnosis (T0) and after four weeks of steroid treatment (T4). MicroRNA profiles were analyzed using next generation sequencing, and selected significantly differentially expressed miRNAs were validated by quantitative reverse transcription-polymerase chain reaction. In detail, 18 miRNAs were differentially expressed from T0 to T4, 16 of which were upregulated and 2 of which were downregulated. Out of these, three miRNAs (miR-144, miR-142, and miR-96) could putatively recognize the 3’UTR of the GR gene and three miRNAs (miR-363, miR-96, miR-142) contained GREs sequences, thereby potentially enabling direct regulation by the GR. In conclusion, we identified miRNAs differently expressed during GC treatment and miRNAs which could be directly regulated by GCs in blood cells of young IBD patients. These results could represent a first step towards their translation as pharmacogenomic biomarkers.

VL - 19 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29738455?dopt=Abstract ER -