The role of miR-221 and miR-200a in pterygium pathogenesis.

• Main Authors: Chueh-Wei Wu, 吳雀維
• Other Authors: Chung-Hung Tsai
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/27261667744019598298

博士 === 中山醫學大學 === 醫學研究所 === 104 === Pterygium is a common ocular disease of which the exact pathogenesis is still unclear. In general, pterygium has a strong correlation with UV exposure. The characteristics of pterygium are very similar to the proliferation of tumor cells, and the abnormalities in p53 gene and protein expression in pterygia tissues is also very similar to tumor tissues. Changes of microRNAs in tumor formation may also be involved in the development of pterygium. MicroRNAs are small non coding RNAs that have been implicated in tumor development. Previous studies show that microRNAs can regulate the expression of cell cycles and the associate genes of cancerous cells, including ras、Rb、 p53、p21 and myc. We collected 120 pterygial and 120 normal conjunctival samples for this study. Immunohistochemistry, real-time reverse transcription (RT)–PCR, and pterygium cell line (PECs) cell models were performed to determine and confirm the effect of β-catenin protein localization, miR-221, p27Kip1 gene expression, p53, p53 down-stream EMT associated protein and miR-200a. 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 the β-catenin-nuclear/cytoplasmic-positive groups than in the β-catenin membrane-positive and negative groups (p=0.001). We also found that p27Kip1 gene expression in pterygium correlated negatively with miR-221 expression (p=0.002). The expression of miR-200a in pterygium tissues was significantly lower than in the conjunctiva controls (Ratio＜0.5,p =0.015). Up-regulated miR-200a levels correlated positively with p53 protein expression (p <0.001). MiR-200a downstream ZEB1/ZEB1 protein expression correlated negatively with miR-200a expression. Cell model studies demonstrated that miR-200a controlled the EMT of PECs through up-regulated ZEB1, ZEB2 and Snail gene expression. Our study demonstrated that activation of β-catenin in pterygium may interact with miR-221, resulting in p27Kip1 gene downregulation that influences pterygium pathogenesis, and the expression of miR-200a plays an important role in EMT processing.