The role of long noncoding RNAs in ocular angiogenesis and vascular oculopathy

Figures

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  Fig. 1. Nuclear Mechanisms of lncRNAs. Scaffold lncRNA can serve as a structural scaffold for histone or DNA modification enzymes to regulate target gene transcription. Decoy lncRNA can act as decoy by sequestering transcription factor away from its promoter region. Guide lncRNA can guide transcription factor to its promoter region by binding to both DNA and the transcription factor. Signal lncRNAs can be induced by signals or stressors and attract transcription factors to its target gene promoter region

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  Fig. 2. Cytoplasmic mechanisms of LncRNAs. A) LncRNAs can interact with 3’-untranslated region (UTR) binding proteins which impact mRNA stability. B) Antisense lncRNAs regulate mRNA stability by forming duplexes with mRNA through complementary base pairing C) LncRNAs can have microRNA (miRNA)-complementary sites that act as competitive endogenous RNAs (ceRNAs) and sequester miRNAs away from their targets D) LncRNAs regulate protein translation and affect post-translational mechanisms. E) LncRNAs code for regulatory micro-peptides. F) LncRNAs regulate signaling pathways in the cytoplasm

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  Fig. 3. ANRIL lncRNA Promotes inflammation by regulating NF-kB pathway and enhances VEGF expression and angiogenesis through interacting with p300 and EZH2, which regulates miR200b. The target sequence in VEGFA that is complementary to miR200b seed region is CAGUAUU (1314–1320) in VEGFA 3’UTR

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  Fig. 4. HOTAIR lncRNA promotes angiogenesis by binding to PRC2 and LSD, which regulates VEGF-A, ANGPTL4, PFGF and HIF1α transcription

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  Fig. 5. HOTTIP lncRNA promotes inflammation and angiogenesis by activating p38/MAPK pathway, as well as by interacting with WDR5 and MLL, which regulates ICAM-1 and VEGF transcription

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  Fig. 6. H19 lncRNA Inhibits endMT by inhibiting TGF-β1 and MAPK-ERK1/2 pathway; inhibits inflammation by sponging miR-19b that targets SIRT1; enhances angiogenesis by sponging miR-29c that targets VEGF-A. The target sequence in SIRT1 that is complementary to miR-19-3p seed region is UUGCAC (1285–1291) in SIRT1 3’UTR. The target sequence in VEGFA that is complementary to miR-29c seed region is UGGUGCUA (1758–1765) in VEGFA 3’UTR

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  Fig. 7. IPW lncRNA enhances angiogenesis by repressing miR-370 at the DLK1-DIO3 locus, which targets KDR and BMP-2. The target sequence in KDR that is complementary to miR-370 seed region is CAGCAGG (79–86) in KDR 3’UTR. The target sequence in BMP-2 that is complementary to miR-370 seed region is AGCAGG (725–731) in BMP-2 3’UTR

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  Fig. 8. MALAT1 lncRNA promotes angiogenesis by acting as ceRNA for miR203a-3p, miR-205-5p, miR-124-3p, and miR-320 that target VEGF, HIF1α and EGR1, and promotes inflammation by elevating IL-1β, IL-6 and TNF-α levels. The target sequences in HIF1α that is complementary to miR-320a and miR-203a seed region are AGCUUU (1846–1852) and AUUUCA (995–1001) in HIF1α 3’UTR. The target sequences in VEGFA that is complementary to miR-205-5p and miR-203-3p seed regions are AUGAAGG (167–173) and AUUUCA (1320–1326) in VEGFA 3’UTR. The target sequence in EGR1 that is complementary to miR-124-3p seed region is GUGCCUU (769–775) in EGR1 3’UTR

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  Fig. 9. MIAT lncRNA promotes angiogenesis by acting as ceRNA for mirR-150-5p that targets VEGF. The target sequences in VEGFA that is complementary to miR-150-5p seed region are UUGGGA (676–681) and GGGGA (789–794) in VEGFA 3’UTR

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  Fig. 10. NEAT1 lncRNA enhances angiogenesis by acting as ceRNA for miR-19-5p that targets TGB-βR2 and therefore enhancing VEGF-A expression. It also prevents resolving inflammation by inhibiting M2 macrophage polarization by acting ceRNA for miRNA-148a-3p that targets PTEN. The target sequences in PTEN that is complementary to miR-148-3p seed region are UGCACUG (2254–2260) and UGCACUG (3151–3158) in PTEN 3’UTR. The target sequence in TGF-βR2 that is complementary to miR-17-5p seed region is GCACUUU (268–275) in TGF-βR2 3’UTR

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  Fig. 11. TUG lncRNA enhances angiogenesis by acting as ceRNA for miR-34a-5p and miR-299 that targets VEGF, miR-204-5p that targets JAK2, miR-145-5p that targets CCN1 and miR-29c-3p that targets PDGF-BB. It also promotes inflammation by elevating TNF-α, IL-1β and IL-6. The target sequences in VEGFA that is complementary to miR-34-5p and miR-299-3p seed regions are CACUGCC (859–865) and CCCACAU in VEGFA 3’UTR. The target sequence in JAK2 that is complementary to miR-204-5p seed region is AAGGGA (1453–1459) in JAK2 3’UTR. The target sequence in CCN1 that is complementary to miR-145-5p seed region is ACUGGA (572–577) in CCN1 3’UTR. The target sequence in PDGFB that is complementary to miR-29c-3p seed region is UGGUGCU (132–138) in PDGFB 3’UTR

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  Fig. 12. MEG3 lncRNA represses angiogenesis by acting as ceRNA for miR-6720-5p that targets CYB5R2, ceRNA for miR-9, and by inhibiting TGF-β and VEGF expression. The target sequences in CYB5R2 that is complementary to miR-6720-5p seed region are GGCUGGAA (57–64), GGGCUGGA (398–404) and GGCUGGAA (434–441) in CYB5R2 3’UTR