title: Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are important post-transcriptional regulators. Altered expression of miRNAs has recently demonstrated association with human ulcerative colitis (UC). In this study, we attempted to elucidate the roles of miR-126 in the pathogenesis of UC.
  
  
  METHODS
  Expression of miR-126, miR-21, miR-375 and the potential targets NF-κB inhibitor alpha (IκBα, IKBA or NFKBIA), Polo-like kinase 2 (PLK2) and v-Crk sarcoma virus CT10 oncogene homolog (CRK) were assessed in 52 colonic biopsies from patients with active UC, inactive UC, irritable bowel syndrome (IBS) and from healthy subjects by quantitative RT-PCR and immunofluorescence analyses. Regulation of gene expression by miR-126 was assessed using luciferase reporter construct assays and specific miRNA mimic transfection.
  
  
  RESULTS
  We found that the expression of miR-126 and miR-21 were significantly increased in active UC group compared to the inactive UC, IBS and healthy control groups (P<0.05). In contrast, the expression of IKBA mRNA and protein was remarkably decreased in the active UC group compared with the other three groups (P<0.05). The expression of miR-126 and IKBA mRNA were inversely correlated in active UC patients (P<0.05). However the expression of miR-375, PLK2 and CRK showed no difference between each group. Furthermore, we demonstrate that endogenous miR-126 and exogenous miR-126 mimic can inhibit IκBα expression. Finally, mutating the miR-126 binding site of the IKBA 3'-UTR reporter construct restored reporter gene expression.
  
  
  CONCLUSIONS
  miR-126 may play roles in UC inflammatory activity by down-regulating the expression of IKBA, an important inhibitor of NF-κB signaling pathway.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Guan
authors.forename: Wenkai
authors.initials: W
authors.lastname: Tan
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.forename: Guoli
authors.initials: G
authors.lastname: Wei
authors.forename: Weiyun
authors.initials: W
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D020672:I-kappa B Proteins; C527111:MIRN126 microRNA, human; C524940:MIRN21 microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha