Inactivation of p53 in pterygium influence miR-200a expression resulting in ZEB1/ZEB2 up-regulation and EMT processing.
Loss of p53 function has been linked to progression of pterygium. MiR-200a is known to be controlled by p53. Here, we hypothesize that expression of miR-200a and downstream ZEB1/ZEB2 genes are regulated epithelial-mesenchymal transition (EMT) involved in the pathogenesis and recurrence of pterygium. For this study, 120 primary pterygial samples were collected. Immunohistochemistry and real-time RT-PCR were performed to determine the expression of p53, p53 down-stream EMT associated protein and miR-200a. The molecular correlation of p53, miR-200a and downstream genes were confirmed using primary pterygium cells (PECs). Expression of miR-200a in pterygium tissues was significantly lower than in conjunctiva controls (p = 0.015). Up-regulated miR-200a levels were positively correlated with and p53 protein expression (p < 0.001). The miR-200a downstream ZEB1/ZEB1 protein expression were negative correlated 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 inactivation of p53 in pterygium may influence miR-200a, resulting in ZEB1/ZEB2 up-regulation and EMT processing of pterygium. Therefore, we suggest that expression of miR-200a play an important role in EMT processing and recurrence of pterygium.
['Wu|Chueh-Wei|CW|', 'Peng|Mei-Ling|ML|', 'Yeh|Ken-Tu|KT|', 'Tsai|Yi-Yu|YY|', 'Chiang|Chun-Chi|CC|', 'Cheng|Ya-Wen|YW|']
D000368:Aged D000369:Aged, 80 and over D002460:Cell Line D003228:Conjunctiva D058750:Epithelial-Mesenchymal Transition D005260:Female D018398:Homeodomain Proteins D006801:Humans D007150:Immunohistochemistry D008297:Male D035683:MicroRNAs D008875:Middle Aged D011625:Pterygium D060888:Real-Time Polymerase Chain Reaction D012097:Repressor Proteins D016159:Tumor Suppressor Protein p53 D015854:Up-Regulation D000074165:Zinc Finger E-box Binding Homeobox 2 D000071799:Zinc Finger E-box-Binding Homeobox 1
p53 Pterygium miR-200a EMT