Home LiteratureArticle Details
PMID: 24623407 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Long non-coding RNAs: new players in ocular neovascularization.

Molecular biology reports ·Vol. 41 ·No. 7 ·2014-07-00 ·Pages 4493-505

Xu XD, Li KR, Li XM, Yao J, Qin J, Yan B

Abstract

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.

MeSH Terms
Aged Animals Aqueous Humor/metabolism Female Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Guanylate Cyclase-Activating Proteins/genetics,metabolism Homeodomain Proteins/genetics,metabolism Humans Hyperoxia/genetics,metabolism,pathology MAP Kinase Signaling System Macular Degeneration/genetics,metabolism,pathology Male Mice Middle Aged Neovascularization, Pathologic/genetics,metabolism,pathology Oligonucleotide Array Sequence Analysis Protein Isoforms/genetics,metabolism RNA, Long Noncoding/genetics,metabolism RNA, Messenger/genetics,metabolism Retina/metabolism,pathology
Chemicals
Guanylate Cyclase-Activating Proteins Homeodomain Proteins Protein Isoforms RNA, Long Noncoding RNA, Messenger VAX2 protein, human
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xu Xue-Dong
Eye Hospital, Nanjing Medical University, 138# Han-Zhong Road, Nanjing, 210029, China.
Li Ke-Ran
Li Xiu-Miao
Yao Jin
Qin Jiang
Yan Biao
References (38)
38 references, click to expand
  1. Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network.
    Nucleic Acids Res. 2011 May;39(9):3864-78 PMID: 21247874
  2. Long non-coding RNAs: modulators of nuclear structure and function.
    Curr Opin Cell Biol. 2014 Feb;26:10-8 PMID: 24529241
  3. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W169-75 PMID: 17576678
  4. MAPK signaling regulates endothelial cell assembly into networks and expression of MT1-MMP and MMP-2.
    Am J Physiol Cell Physiol. 2005 Mar;288(3):C659-68 PMID: 15509661
  5. Multimeric assembly and biochemical characterization of the Trax-translin endonuclease complex.
    Nat Struct Mol Biol. 2011 Jun;18(6):658-64 PMID: 21552261
  6. Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence.
    Genome Res. 2011 Feb;21(2):203-15 PMID: 21177969
  7. NF-kappaB signaling as a putative target for omega-3 metabolites in the prevention of age-related macular degeneration (AMD).
    Exp Gerontol. 2009 Nov;44(11):685-8 PMID: 19751815
  8. Animal models of choroidal and retinal neovascularization.
    Prog Retin Eye Res. 2010 Nov;29(6):500-19 PMID: 20488255
  9. New insight into the functioning of nitric oxide-receptive guanylyl cyclase: physiological and pharmacological implications.
    Mol Cell Biochem. 2010 Jan;334(1-2):221-32 PMID: 20012469
  10. Molecular mechanisms of long noncoding RNAs.
    Mol Cell. 2011 Sep 16;43(6):904-14 PMID: 21925379
  11. The mouse retina as an angiogenesis model.
    Invest Ophthalmol Vis Sci. 2010 Jun;51(6):2813-26 PMID: 20484600
  12. Mediators of ocular angiogenesis.
    J Genet. 2009 Dec;88(4):495-515 PMID: 20090210
  13. Controlling gene expression in response to stress.
    Nat Rev Genet. 2011 Nov 03;12(12):833-45 PMID: 22048664
  14. Nuclear factor-kappaB activation: from bench to bedside.
    Exp Biol Med (Maywood). 2008 Jan;233(1):21-31 PMID: 18156302
  15. Long noncoding RNAs and human disease.
    Trends Cell Biol. 2011 Jun;21(6):354-61 PMID: 21550244
  16. Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-alpha, vascular endothelial growth factor and platelet-derived growth factor.
    Angiogenesis. 1998;2(1):93-104 PMID: 14517379
  17. lincRNAs: genomics, evolution, and mechanisms.
    Cell. 2013 Jul 3;154(1):26-46 PMID: 23827673
  18. Molecular mechanisms and clinical applications of angiogenesis.
    Nature. 2011 May 19;473(7347):298-307 PMID: 21593862
  19. Ocular angiogenesis: mechanisms and recent advances in therapy.
    Adv Clin Chem. 2010;50:103-21 PMID: 20521443
  20. Crosstalk in NF-κB signaling pathways.
    Nat Immunol. 2011 Jul 19;12(8):695-708 PMID: 21772278
  21. Regulation and function of NF-kappaB transcription factors in the immune system.
    Annu Rev Immunol. 2009;27:693-733 PMID: 19302050
  22. Ocular neovascularization.
    J Mol Med (Berl). 2013 Mar;91(3):311-21 PMID: 23329331
  23. The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity.
    Neural Dev. 2011 Sep 21;6:32 PMID: 21936910
  24. Guanylyl cyclase structure, function and regulation.
    Cell Signal. 2011 Dec;23(12):1921-6 PMID: 21914472
  25. Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis.
    Development. 2011 Oct;138(20):4451-63 PMID: 21880786
  26. Microarray technology: beyond transcript profiling and genotype analysis.
    Nat Rev Genet. 2006 Mar;7(3):200-10 PMID: 16485019
  27. The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.
    Biochim Biophys Acta. 2011 Sep;1813(9):1619-33 PMID: 21167873
  28. Oxygen-induced retinopathy in the mouse.
    Invest Ophthalmol Vis Sci. 1994 Jan;35(1):101-11 PMID: 7507904
  29. The long noncoding RNA RNCR2 directs mouse retinal cell specification.
    BMC Dev Biol. 2010 May 11;10:49 PMID: 20459797
  30. Long noncoding RNA in genome regulation: prospects and mechanisms.
    RNA Biol. 2010 Sep-Oct;7(5):582-5 PMID: 20930520
  31. Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice.
    Biochem Biophys Res Commun. 2010 Jan 8;391(2):1268-73 PMID: 20006575
  32. Identification of PatL1, a human homolog to yeast P body component Pat1.
    Biochim Biophys Acta. 2007 Dec;1773(12):1786-92 PMID: 17936923
  33. TRANSFAC: a database on transcription factors and their DNA binding sites.
    Nucleic Acids Res. 1996 Jan 1;24(1):238-41 PMID: 8594589
  34. Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανβ3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells.
    Cell Signal. 2014 Jan;26(1):133-40 PMID: 24063814
  35. Tightly bound to DNA proteins: possible universal substrates for intranuclear processes.
    Gene. 2012 Jan 15;492(1):54-64 PMID: 22001404
  36. Pathological roles of MAPK signaling pathways in human diseases.
    Biochim Biophys Acta. 2010 Apr;1802(4):396-405 PMID: 20079433
  37. The long noncoding RNA Vax2os1 controls the cell cycle progression of photoreceptor progenitors in the mouse retina.
    RNA. 2012 Jan;18(1):111-23 PMID: 22128341
  38. catRAPID omics: a web server for large-scale prediction of protein-RNA interactions.
    Bioinformatics. 2013 Nov 15;29(22):2928-30 PMID: 23975767
Article Info
Journal
Molecular biology reports
Abbr.
Mol Biol Rep
ISSN
1573-4978
Published
2014-07-00
Epub
2014-00-13
Pages
4493-505
Language
English
Region
Netherlands
NLM ID
0403234
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com