High-throughput sequencing of microRNAs in glucocorticoid sensitive paediatric inflammatory bowel disease patients

Sara De Iudicibus, Marianna Lucafò, Nicola Vitulo, Stefano Martelossi, Rosanna Zimbello, Fabio De Pascale, Claudio Forcato, Samuele Naviglio, Alessia Di Silvestre, Marco Gerdol, Gabriele Stocco, Giorgio Valle, Alessandro Ventura, Matteo Bramuzzo, Giuliana Decorti

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number1399
JournalInternational Journal of Molecular Sciences
Volume19
Issue number5
DOIs
Publication statusPublished - May 8 2018

Keywords

  • Glucocorticoids
  • Inflammatory bowel disease
  • mRNA
  • Pediatric patients

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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