Molecular vision · 2014
MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in pterygium pathogenesis.
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Wu Chueh-Wei, Cheng Ya-Wen, Hsu Nan-Yung, Yeh Ken-Tu, Tsai Yi-Yu, Chiang Chun-Chi, Wang Wei-Ran, Tung Jai-Nien
Аннотация
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.
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.