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Mol Vis. 2014 Jul 21;20:1048-56. eCollection 2014.

MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in pterygium pathogenesis.

Author information

1
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Pharmacology, Chung Shan Medical University Hospital.
2
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
3
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
4
Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
5
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;
6
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.

Abstract

PURPOSE:

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.

PMID:
25053875
PMCID:
PMC4105113
[Indexed for MEDLINE]
Free PMC Article

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