Down-Regulation of MicroRNA-184 Is Associated With Corneal Neovascularization

作者:Zong, Rongrong; Zhou, Tong; Lin, Zhirong; Bao, Xiaorui; Xiu, Yanghui; Chen, Yanfeng; Chen, Longlong; Ma, Jian-xing; Liu, Zuguo; Zhou, Yueping*
来源:Investigative Ophthalmology & Visual Science, 2016, 57(3): 1398-1407.
DOI:10.1167/iovs.15-17417

摘要

PURPOSE. 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 beta-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 beta-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/beta-catenin expression as well as corneal neovascularization, indicating that miR-184 negatively regulates corneal neovascularization.