P760 microRNA expression profiling of inflammatory bowel disease
Sibia C.F.1, Silva R.P.L.*2, Ariede J.R.3, Severino F.E.2, Farinelli E.2, Renosto F.L.2, Sassaki L.Y.2, Reis P.P.2, Hossne R.S.2
1Faculdade de Medicina de Botucatu, Botucatu, São Paulo, Brazil 2Faculdade de Medicina de Botucatu, Botucatu, São Paulo, Brasil, Brazil 3Faculdade de Medicina de Botucatu, Botucatu, Brazil
Crohn's disease (CD) and ulcerative colitis (UC) are the two major diseases that make up the inflammatory bowel disease (IBD). The etiology is multifactorial, is an interaction between individual genetic characteristics, predisposition and environment. These factors must be involved in the modification of the immune response with consequent formation of altered inflammatory response. Studies indicate that several genes, in addition to those involved in the modulation of the immune response, are differentially expressed in patients with CD. vsUC. Considering that microRNAs (miRNAs) are important gene expression regulators with a role in human diseases, including inflammatory and chronic degenerative diseases, they may be good candidates to investigate as biomarkers with diagnostic, prognostic and therapeutic applications. An important feature of miRNAs is their stability and reliable detection in body fluids.
A meta-analysis was performed for the identification of miRNA expression data in IBD. Inclusion and exclusion criteria were applied and 10 studies were selected, from which relevant miRNAs with statistically significant, increased or decreased expression as compared to controls were identified. We also collected information on the type and number of analyzed samples (serum, plasma or tissue) with CD or UC, type of platforms used for analysis of global miRNA expression and data validation, author name and date of publication. Significantly deregulated miRNAs were used in bioinformatic analysis to predict the target genes regulated by these miRNAs. Prediction analyzes of miRNA target transcripts and enrichment of biological functions of the target genes were performed.
The results showed 6 CD miRNAs with increased expression and 51 UC. On the other hand, miRNAs with decreased expression were found on 51 CD and 26 UC.
The miRNAs that showed the greatest number of interactions with IBD deregulated genes were let-7a-5p, let-7b-5p and miR-199a-5p, miR-150–5p, miR-362–3p and miR-224- 5p. For patients with RCU, deregulated miRNAs were miR-155–5p, miR-24–5p, miR-335–5p and miR-16–5p. Such miRNAs may play an important role in the molecular mechanisms of disease. In addition, results were used to identify gene interactions and biological processes within inflammation and immune response. Studies such as this may contribute to the identification of miRNAs and target genes as useful biomarkers for the development of new therapeutic strategies for patients with IBD.
miRNA-mRNA networks identified may play important roles in the development and progression of inflammatory bowel disease. Future validation studies with large patient cohorts are required to demonstrate the role of miRNAs and target genes in IBD.