title: Overexpression of miR-125b, a novel regulator of innate immunity, in eosinophilic chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) represents a hard-to-treat subtype of CRS.
  
  
  OBJECTIVE
  To determine the pattern of expression and biologic role of microRNAs (miRNAs) in CRS, particularly in eosinophilic CRSwNP.
  
  
  METHODS
  Global miRNA expression in sinonasal mucosa from controls, CRS without nasal polyps (CRSsNP), and patients with eosinophilic CRSwNP was compared using miRNA microarrays. MiR-125b expression was detected by means of quantitative reverse-transcriptase polymerase chain reaction. The cellular localization of miR-125b was determined by in situ hybridization. MiR-125b functional assays were performed on airway epithelial cells and mice. MiR-125b expression regulation was studied by tissue and cell culture.
  
  
  RESULTS
  CRSsNP and eosinophilic CRSwNP exhibited distinct miRNA expression profiles. MiR-125b was specifically up-regulated in eosinophilic CRSwNP. MiR-125b was mainly expressed by sinonasal and bronchial epithelial cells. EIF4E-binding protein 1 (4E-BP1) was identified as a direct target of miR-125b. MiR-125b mimic or inhibitor enhanced or decreased IFN-α/β production elicited by dsRNA in vitro or in vivo, respectively. 4E-BP1 expression was decreased, whereas IFN regulatory factor-7 and IFN-β expression was increased, in eosinophilic CRSwNP. IFN-β mRNA levels positively correlated with IL-5 mRNA levels and eosinophil infiltration in sinonasal mucosa. IFN-β stimulated B cell-activating factor of the tumor necrosis factor family production in airway epithelial cells. miR-125b could be induced by lipopolysaccharide, dsRNA, and IL-10.
  
  
  CONCLUSIONS
  The up-regulated expression of miR-125b may enhance type I IFN expression through suppressing 4E-BP1 protein expression in airway epithelial cells, which potentially contributes to mucosal eosinophilia in eosinophilic CRSwNP.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Xin-Hao
authors.initials: XH
authors.lastname: Zhang
authors.forename: Ya-Na
authors.initials: YN
authors.lastname: Zhang
authors.forename: Hua-Bin
authors.initials: HB
authors.lastname: Li
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Hu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Cao
authors.forename: Bo
authors.initials: B
authors.lastname: Liao
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Cui
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007155:Immunologic Factors / Q000097:blood; D017403:In Situ Hybridization; D016898:Interferon-alpha / Q000097:blood; D016899:Interferon-beta / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009298:Nasal Polyps / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D016898:Interferon-alpha; D015848:Interleukin-5; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016753:Interleukin-10; D016899:Interferon-beta