title: Inactivation of p53 in pterygium influence miR-200a expression resulting in ZEB1/ZEB2 up-regulation and EMT processing.
abstract: 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pharmacology, Chung Shan Medical University Hospital, Taichung, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chueh-Wei
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Peng
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ken-Tu
authors.initials: KT
authors.lastname: Yeh
authors.affiliation: Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Tsai
authors.affiliation: Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: ywc@tmu.edu.tw.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D003228:Conjunctiva / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011625:Pterygium / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: EMT; Pterygium; miR-200a; p53