Long non-coding RNAs: new players in ocular neovascularization
- 665 Downloads
Pathological neovascularization are the most prevalent causes of moderate or severe vision loss. Long non-coding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in numerous biological processes and complicated diseases. However, the role of lncRNAs in ocular neovascularization is still unclear. Here, we constructed a murine model of ocular neovascularization, and determined lncRNA expression profiles using microarray analysis. We identified 326 or 51 lncRNAs that were significantly either up-regulated or down-regulated in the vaso-obliteration or neovascularization phase, respectively. Based on Pearson correlation analysis, lncRNAs/mRNAs co-expression networks were constructed. GO enrichment analysis of lncRNAs-co-expressed mRNAs indicated that the biological modules were correlated with chromosome organization, extracellular region and guanylate cyclase activator activity in the vaso-obliteration phase, and correlated with cell proliferation, extracellular region and guanylate cyclase regulator activity in the neovascularization phase. KEGG pathway analysis indicated that MAPK signaling was the most significantly enriched pathway in both phases. Importantly, Vax2os1 and Vax2os2 were not only dynamically expressed in the vaso-obliteration and neovascularization phases, but also significantly altered in the aqueous humor of patients with neovascular age-related macular degeneration (AMD), suggesting a potential role of lncRNAs in the regulation of ocular neovascularization. Taken together, this study provided novel insights into the molecular pathogenesis of ocular neovascularization. The intervention of dysregulated lncRNA could become a potential target for the prevention and treatment of ocular vascular diseases.
KeywordsLong non-coding RNA Ocular neovascularization Microarray analysis Age-related macular degeneration
This work was generously supported by grants from the National Natural Science Foundation of China (Grant No. 81300241 to B.Y. and Grant No. 81371055 to Q.J.), grants from the National clinical key construction project [Grant No. (2012) 649 to Q.J.], and grants from the Medical Science and Technology Development Project Fund of Nanjing (Grant No. ZKX 12047 to Q.J., Grant No. YKK12207 to G.F.-C., and Grant No. YKK12208 to J.Y.).
- 12.da Huang W, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, Guo Y, Stephens R, Baseler MW, Lane HC, Lempicki RA (2007) DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 35:W169–W175PubMedCentralCrossRefPubMedGoogle Scholar
- 16.Berezikov E, Robine N, Samsonova A, Westholm JO, Naqvi A, Hung JH, Okamura K, Dai Q, Bortolamiol-Becet D, Martin R, Zhao Y, Zamore PD, Hannon GJ, Marra MA, Weng Z, Perrimon N, Lai EC (2011) Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence. Genome Res 21:203–215PubMedCentralCrossRefPubMedGoogle Scholar
- 25.Armstrong D, Ueda T, Ueda T, Aljada A, Browne R, Fukuda S, Spengler R, Chou R, Hartnett M, Buch P, Dandona P, Sasisekharan R, Dorey CK (1998) Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-α, vascular endothelial growth factor and platelet-derived growth factor. Angiogenesis 2:93–104CrossRefPubMedGoogle Scholar
- 30.Stenzel D, Lundkvist A, Sauvaget D, Busse M, Graupera M, van der Flier A, Wijelath ES, Murray J, Sobel M, Costell M, Takahashi S, Fässler R, Yamaguchi Y, Gutmann DH, Hynes RO, Gerhardt H (2011) Integrin-dependent and-independent functions of astrocytic fibronectin in retinal angiogenesis. Development 138:4451–4463PubMedCentralCrossRefPubMedGoogle Scholar