title: MicroRNA profiling in mucosal biopsies of eosinophilic esophagitis patients pre and post treatment with steroids and relationship with mRNA targets.
abstract: BACKGROUND
  The characterization of miRNAs and their target mRNAs involved in regulation of the immune process is an area of intense research and relatively little is known governing these processes in allergic inflammation. Here we present novel findings defining the miRNA and mRNA transcriptome in eosinophilic esophagitis (EoE), an increasing recognized allergic disorder.
  
  
  METHODS
  Esophageal epithelial miRNA and mRNA from five paired biopsies pre- and post-treatment with glucocorticosteroids were profiled using Taqman and Affymetrix arrays. Validation was performed on additional paired biopsies, untreated EoE specimens and normal controls. Differentially regulated miRNAs and mRNAs were generated, within which miRNA-mRNA target pairs with high predicted confidence were identified.
  
  
  RESULTS
  Compared to the post-glucocorticoid treated esophageal mucosa, of all the 377 miRNA sequences examined, 32 miRNAs were significantly upregulated and four downregulated in the pre-treated biopsies. MiR-214 was the most upregulated (150 fold) and miR-146b-5b, 146a, 145, 142-3p and 21 were upregulated by at least 10 fold. Out of 12 miRNAs chosen for validation by qRT-PCR, five (miR-214, 146b-5p, 146a, 142-3p and 21) were confirmed and 11 shared the same trend. When the expression of the 12 miRNAs in the EoE mucosa was compared to unrelated normal mucosa, six (miR-214, 146b-5p, 146a, 21, 203, and 489) showed similar significant changes as in the paired samples and 10 of them shared the same trend. In the same five pairs of samples used to profile miRNA, 311 mRNAs were down-regulated and 35 were up-regulated in pre-treated EoE mucosa. Among them, 164 mRNAs were identified as potential targets of differentially regulated miRNAs. Further analysis revealed that immune-related genes, targeted and non-targeted by miRNAs, were among the most important genes involved in the pathogenesis of EoE.
  
  
  CONCLUSIONS
  Our findings add to the accumulating body of data defining a regulatory role for miRNA in immune and allergic processes.
authors: Department of Pathology and Laboratory Medicine, Rhode Island Hospital, the Alpert School of Medicine, Brown University, Providence, Rhode Island, United States of America.
authors: Shaolei
authors: S
authors: Lu
authors: Vincent A
authors: VA
authors: Mukkada
authors: Shamlal
authors: S
authors: Mangray
authors: Kelly
authors: K
authors: Cleveland
authors: Nick
authors: N
authors: Shillingford
authors: Christoph
authors: C
authors: Schorl
authors: Alexander S
authors: AS
authors: Brodsky
authors: Murray B
authors: MB
authors: Resnick
mesh_terms: D000293:Adolescent; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D057765:Eosinophilic Esophagitis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000235:genetics; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D013256:Steroids