title: Small non-coding RNA signature in multiple sclerosis patients after treatment with interferon-β.
abstract: BACKGROUND
  Non-coding small RNA molecules play pivotal roles in cellular and developmental processes by regulating gene expression at the post-transcriptional level. In human diseases, the roles of the non-coding small RNAs in specific degradation or translational suppression of the targeted mRNAs suggest a potential therapeutic approach of post-transcriptional gene silencing that targets the underlying disease etiology. The involvement of non-coding small RNAs in the pathogenesis of neurodegenerative diseases such as Alzheimer's , Parkinson's disease and Multiple Sclerosis has been demonstrated. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by chronic inflammation, demyelination and scarring as well as a broad spectrum of signs and symptoms. The current standard treatment for SM is interferon ß (IFNß) that is less than ideal due to side effects. In this study we administered the standard IFN-ß treatment to Relapsing-Remitting MS patients, all responder to the therapy; then examined their sncRNA expression profiles in order to identify the ncRNAs that were associated with MS patients' response to IFNß.
  
  
  METHODS
  40 IFNß treated Relapsing-Remitting MS patients were enrolled. We analyzed the composition of the entire small transcriptome by a small RNA cloning method, using peripheral blood from Relapsing-Remitting MS patients at baseline and 3 and 6 months after the start of IFNß therapy. Real-time qPCR from the same patients group and from 20 additional patients was performed to profile miRNAs expression.
  
  
  RESULTS
  Beside the altered expression of several miRNAs, our analyses revealed the differential expression of small nucleolar RNAs and misc-RNAs.For the first time, we found that the expression level of miR-26a-5p changed related to INF-β response. MiR-26a-5p expression was significantly higher in IFN-β treated RRMS patients at 3 months treatment, keeping quite stable at 6 months treatments.
  
  
  CONCLUSIONS
  Our results might provide insights into the mechanisms of action of IFN-β treatment in MS and provide fundamentals for the development of new biomarkers and/or therapeutic tools.
authors.affiliation: Department of Life Sciences, University of Naples II, Via Vivaldi 43, Caserta 81100, Italy. bruna.defelice@unina2.it.
authors.forename: Bruna
authors.initials: B
authors.lastname: De Felice
authors.forename: Paolo
authors.initials: P
authors.lastname: Mondola
authors.forename: Anna
authors.initials: A
authors.lastname: Sasso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Orefice
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bresciamorra
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
authors.forename: Elio
authors.initials: E
authors.lastname: Biffali
authors.forename: Marco
authors.initials: M
authors.lastname: Borra
authors.forename: Raimondo
authors.initials: R
authors.lastname: Pannone
mesh_terms: D000293:Adolescent; D000328:Adult; D019295:Computational Biology; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015723:Gene Library; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D055815:Young Adult
chemical_list: D000076122:Disks Large Homolog 4 Protein; D016899:Interferon-beta; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D058727:RNA, Small Untranslated; C501444:DLG4 protein, human; C528163:MIRN26 microRNA, human