title: Down-Regulation of MicroRNA-184 Is Associated With Corneal Neovascularization.
abstract: OBJECTIVE
  Although microRNA-184 (miR-184) is abundantly expressed in the corneas, the role of miR-184 in corneal neovascularization remains unknown. Here we investigated the association between miR-184 expression and corneal neovascularization.
  
  
  METHODS
  Quantitative real-time PCR assay was conducted to detect the expression of miR-184 and its potential target genes in the corneal epithelium of rats with corneal suture-induced neovascularization. MicroRNA-184 was also applied topically to the suture rats. Mimic and inhibitor of miR-184 were transfected into the cultured human umbilical vein endothelial cells (HUVECs), human corneal epithelial (HCE) cells, and simian choroidal endothelial cells (RF/6A). The following experiments were performed to evaluate the effects of miR-184 in these transfected cells: cell proliferation by cell viability assay, cell migration by a scratch wound test, VEGF-induced tube formation, and VEGF and β-catenin levels by Western blot analysis.
  
  
  RESULTS
  The expression of miR-184 was significantly reduced, whereas the gene expression of frizzled-4, a receptor of the Wnt pathway, was up-regulated in the corneal epithelium of corneal suture rats. The corneal neovascularization induced by suture was ameliorated by topical administration of miR-184. In the cells transfected with mimic and inhibitor of miR-184, miR-184 significantly suppressed the cell proliferation and cell migration of HUVECs, miR-184 down-regulated VEGF, and β-catenin expression in HUVECs and HCE cells. Furthermore, miR-184 inhibited the tube formation of RF/6A cells.
  
  
  CONCLUSIONS
  Down-regulation of miR-184 is associated with up-regulation of VEGF and Wnt/β-catenin expression as well as corneal neovascularization, indicating that miR-184 negatively regulates corneal neovascularization.
authors.affiliation: Eye Institute of Xiamen University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zong
authors.affiliation: Department of Pharmacy, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, Fujian, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Xiamen Eye Center Affiliated to Xiamen University, Xiamen, Fujian, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Eye Institute of Xiamen University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Bao
authors.affiliation: Xiamen Eye Center Affiliated to Xiamen University, Xiamen, Fujian, China 4Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Xiu
authors.affiliation: Eye Institute of Xiamen University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Xiamen Eye Center Affiliated to Xiamen University, Xiamen, Fujian, China.
authors.forename: Longlong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Jian-xing
authors.initials: JX
authors.lastname: Ma
authors.affiliation: Eye Institute of Xiamen University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China 3Xiamen Eye Center Affiliated to Xiamen University, Xiamen, Fujian, China.
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Eye Institute of Xiamen University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016510:Corneal Neovascularization / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C534424:MIRN184 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger