title: Integration of MicroRNA databases to study MicroRNAs associated with multiple sclerosis.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs which regulate many genes post-transcriptionally. In various contexts of medical science, miRNAs gained increasing attention over the last few years. Analyzing the functions, interactions and cellular effects of miRNAs is a very complex and challenging task. Many miRNA databases with diverse data contents have been developed. Here, we demonstrate how to integrate their information in a reasonable way on a set of miRNAs that were found to be dysregulated in the blood of patients with multiple sclerosis (MS). Using the miR2Disease database, we retrieved 16 miRNAs associated with MS according to four different studies. We studied the predicted and experimentally validated target genes of these miRNAs, their expression profiles in different blood cell types and brain tissues, the pathways and biological processes affected by these miRNAs as well as their regulation by transcription factors. Only miRNA-mRNA interactions that were predicted by at least seven different prediction algorithms were considered. This resulted in a network of 1,498 target genes. In this network, the MS-associated miRNAs hsa-miR-20a-5p and hsa-miR-20b-5p occurred as central hubs regulating about 500 genes each. Strikingly, many of the putative target genes play a role in T cell activation and signaling, and many have transcription factor activity. The latter suggests that miRNAs often act as regulators of regulators with many secondary effects on gene expression. Our present work provides a guideline on how information of different databases can be integrated in the analysis of miRNAs. Future investigations of miRNAs shall help to better understand the mechanisms underlying different diseases and their treatments.
authors.affiliation: Department of Neurology, Division of Neuroimmunology, University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Angerstein
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Brigitte Katrin
authors.initials: BK
authors.lastname: Paap
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
authors.forename: Madhan
authors.initials: M
authors.lastname: Thamilarasan
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Thiesen
authors.forename: Uwe Klaus
authors.initials: UK
authors.lastname: Zettl
mesh_terms: D001483:Base Sequence; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs