title: MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in pterygium pathogenesis.
abstract: OBJECTIVE
  MiRNAs are small noncoding RNAs that have been implicated in tumor development. They regulate target gene expression either by mRNA degradation or by translation repression. Activation of β-catenin has been linked to pterygium progression. Here, we hypothesize that β-catenin-associated miRNA, miRNA-221, and downstream p27Kip1 gene expression are correlated with the pathogenesis of pterygium.
  
  
  METHODS
  We collected 120 pterygial and 120 normal conjunctival samples for this study. Immunohistochemistry and real-time reverse transcription (RT)-PCR were performed to determine β-catenin protein localization, miR-221, and p27Kip1 gene expression. Pterygium cell line (PECs) cell models were used to confirm the effect of β-catenin, miR-221, and p27Kip1 gene in the proliferation of pterygium cells.
  
  
  RESULTS
  Seventy-two (60.0%) pterygial specimens showed high miR-221 expression levels, which was significantly higher than the control groups (13 of 120, 10.8%, p<0.0001). MiR-221 expression was significantly higher in β-catenin-nuclear/cytoplasmic-positive groups than in β-catenin membrane-positive and negative groups (p=0.001). We also found that p27Kip1 gene expression in pterygium was negatively correlated with miR-221 expression (p=0.002). In the clinical association, miR-221 expression was significantly higher in the fleshy and intermediate groups than in the atrophic group (p=0.007). The association of miR-221, p27Kip1 and proliferation of pterygium were also confirmed in the PECs model.
  
  
  CONCLUSIONS
  Our study demonstrated that activation of β-catenin in pterygium may interact with miR-221, resulting in p27Kip1 gene downregulation that influences pterygium pathogenesis.
authors: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Pharmacology, Chung Shan Medical University Hospital.
authors: Chueh-Wei
authors: CW
authors: Wu
authors: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Ya-Wen
authors: YW
authors: Cheng
authors: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors: Nan-Yung
authors: NY
authors: Hsu
authors: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
authors: Ken-Tu
authors: KT
authors: Yeh
authors: Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
authors: Yi-Yu
authors: YY
authors: Tsai
authors: Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
authors: Chun-Chi
authors: CC
authors: Chiang
authors: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;
authors: Wei-Ran
authors: WR
authors: Wang
authors: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan ; Department of Neurosurgery, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors: Jai-Nien
authors: JN
authors: Tung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D049109:Cell Proliferation; D003228:Conjunctiva / Q000378:metabolism / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D021381:Protein Transport; D011625:Pterygium / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; D012333:RNA, Messenger; D051176:beta Catenin; C525709:MIR221, human