FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4376270747> ?p ?o ?g. }

• W4376270747 endingPage "239" @default.
• W4376270747 startingPage "237" @default.
• W4376270747 abstract "Journal of Ocular Pharmacology and TherapeuticsVol. 39, No. 4 EditorialFree AccessRibonucleic Acid (RNA) Therapeutics: Role of Long Noncoding RNAs in Ocular Vascular DiseasesShusheng WangShusheng WangAddress correspondence to: Prof. Shusheng Wang, Department of Cell and Molecular Biology, Department of Ophthalmology, Tulane Personalized Health Institute Tulane University, New Orleans, LA 70118, USA E-mail Address: swang1@tulane.eduDepartment of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, USA.Department of Ophthalmology, Tulane University, New Orleans, Louisiana, USA.Department of Tulane Personalized Health Institute, Tulane University, New Orleans, Louisiana, USA.Search for more papers by this authorPublished Online:10 May 2023https://doi.org/10.1089/jop.2023.29104.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail The recent annotation of the complete sequence of human genome totals ∼64,000 genes, of which about 20,000 genes are predicted to be protein coding.1 This indicates that ∼69% of human genes are transcribed as noncoding ribonucleic acids (ncRNAs). Two major classes of ncRNAs include the well-studied microRNAs (miRNAs) and the recently identified long ncRNAs (lncRNAs), which are defined as ncRNAs longer than 200 nucleotides that do not encode proteins. Compared with mRNAs, lncRNAs tend to show lower expression, poorer sequence conservation, and more specific tissue expression patterns. LncRNAs are more often localized in the nucleus than in the cytoplasm and have diverse functional mechanisms.In the nucleus, lncRNAs can function in cis or in trans to influence gene transcription by functioning as scaffold, decoy, guide, or signal to regulate chromatin remodeling.2 Cytoplasmic lncRNAs can regulate mRNA stability and translation by interacting with RNA-binding protein, acting as antisense RNA to regulate mRNA stability, acting as competitive endogenous RNAs (ceRNAs) or “sponges” for miRNAs, regulating protein translation and affecting post-translational mechanisms, or encoding micropeptides. Some lncRNAs are not linear but form covalently closed circles (circRNAs), which will be discussed specifically in future issues.An increasing number of lncRNAs have been linked to ocular vascular diseases in patients or animal models. For example, lncRNAs ANRIL and MIAT1 expression is upregulated in the retina of diabetic or diabetic retinopathy (DR) animals, and in the serum/vitreous or plasma of DR patients.3–8HOTAIR, HIF1A-AS2, and SNHG16 expression is upregulated in the serum/plasma or vitreous of proliferative DR patients.9–15MALAT1 expression is upregulated in the oxygen-induced retinopathy mouse model and diabetic patients,16–19 whereas Vax2os1 and Vax2os2 expression is upregulated in the aqueous humor of wet age-related macular degeneration (AMD) patients.20In contrast, MEG3 expression is downregulated in DR serum and streptozotocin (STZ)-induced diabetic mice,21–24 and PKNY expression is decreased in the retinal pigment epithelium/choroid in a laser-induced choroid neovascularization wet AMD model.25Functionally, studies using animal models have established ANRIL, MIAT1, HOTAIR, and MALAT1 as proangiogenic lncRNAs, whereas MEG3 and PKNY as antiangiogenic lncRNAs. In addition, ANRIL is also proinflammatory and HOTAIR could regulate vascular permeability. Particularly, lncEGFL7OS is a human/primate specific lncRNA that enhances choroid sprouting angiogenesis in human choroid tissue ex vivo.26 These lncRNAs could have therapeutic implications in ocular vascular diseases, including wet AMD, proliferative DR, and retinopathy of prematurity.RNA-based therapies have gained momentum due to the approval of RNA drugs by the FDA in recent years, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and mRNA-based vaccine for coronavirus disease 2019 (Covid-19).27,28 Not surprisingly, many of these technologies could be applied to lncRNAs for preclinical or clinical development. For example, ANRIL and HOTAIR were shown to be proangiogenic and proinflammatory, ASO or siRNAs to these lncRNAs could be tested in models of wet AMD or proliferative DR.For antiangiogenic lncRNAs such as MEG3 and PKNY, their overexpression using adeno-associated viruses or lentiviruses could have therapeutic potential in aforementioned diseases. Similar to mRNA, lncRNAs are susceptible to degradation. However, circRNAs are highly stable as they are protected from exonuclease-mediated degradation. Recently, circRNA vaccines to SARS-CoV2 have been developed, which have shown favorable protection against SARS-CoV2 variants.29 Therefore, developing circ-lncRNA together with lipid nanoparticles delivery could be a potential option for lncRNA overexpression in disease models.As lncRNAs have diverse function mechanisms, the mode of action of lncRNAs should also be considered when designing therapies. For lncRNAs that regulate gene transcription, targeting lncRNA-regulated genomic loci using CRISPR-Cas9, or lncRNA using Cas13, could offer therapeutic opportunities. For example, dCas9-KRAB-mediated targeting of the EGFL7/miR-126/lncEGFL7OS locus has been shown to inhibit the expression of genes in this locus and repress human angiogenic activities in vitro.26 For lncRNAs that provide docking sites or interactional structural elements for miRNAs, DNAs, or proteins, designing small molecules that could interrupt the functional domain of lncRNAs or affect their interaction with partner molecules could have therapeutic implications. For example, small molecules have been designed to target MALAT1 triple helix, which reduced the levels of MALAT1 and its downstream genes.30The future is bright for lncRNA-based therapies in ocular vascular diseases. However, some challenges exist, including undercharacterization of the diverse functions of individual lncRNAs, instability and long-term efficacy of lncRNAs or siRNAs-based therapies, off-target effects of siRNAs, inefficient targeted delivery of negative charged RNAs, and the potential immunogenicity of long RNAs.Author Disclosure StatementNo competing financial interests exist.Funding InformationS.W. was supported by a Startup fund from Tulane University, NIH Grants EY021862 and EY026069, and Brightfocus Grant in age-related macular degeneration (AMD).References1. Nurk S, Koren S, Rhie A, et al. The complete sequence of a human genome. Science 2022;376(6588):44–53; doi: 10.1126/science.abj6987 Crossref, Medline, Google Scholar2. Yu B, Wang S. Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease. Theranostics 2018;8(13):3654–3675; doi: 10.7150/thno.26024 Crossref, Medline, Google Scholar3. Li Q, Pang L, Yang W, et al. Long non-coding RNA of myocardial infarction associated transcript (LncRNA-MIAT) promotes diabetic retinopathy by upregulating transforming growth factor-β1 (TGF-β1) signaling. Med Sci Monit 2018;24:9497–9503; doi: 10.12659/MSM.911787 Crossref, Medline, Google Scholar4. Yan B, Yao J, Liu JY, et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 2015;116(7):1143–1156; doi: 10.1161/CIRCRESAHA.116.305510 Crossref, Medline, Google Scholar5. Zhang J, Chen M, Chen J, et al. Long non-coding RNA MIAT acts as a biomarker in diabetic retinopathy by absorbing. Biosci Rep 2017;37(2):BSR20170036; doi: 10.1042/BSR20170036 Crossref, Medline, Google Scholar6. Yu C, Yang K, Meng X, et al. Downregulation of long noncoding RNA MIAT in the retina of diabetic rats with tail-vein injection of human umbilical-cord mesenchymal stem cells. Int J Med Sci 2020;17(5):591–598; doi: 10.7150/ijms.38078 Crossref, Medline, Google Scholar7. Biswas S, Coyle A, Chen S, et al. Expressions of serum lncRNAs in diabetic retinopathy—A potential diagnostic tool. Front Endocrinol (Lausanne) 2022;13:851967; doi: 10.3389/fendo.2022.851967 Crossref, Medline, Google Scholar8. Wei JC, Shi YL, Wang Q. LncRNA ANRIL knockdown ameliorates retinopathy in diabetic rats by inhibiting the NF-kappaB pathway. Eur Rev Med Pharmacol Sci 2019;23(18):7732–7739; doi: 10.26355/eurrev_201909_18982 Crossref, Medline, Google Scholar9. Wang HS, Wang L, Tang LY, et al. Long noncoding RNA SNHG6 promotes proliferation and angiogenesis of cholangiocarcinoma cells through sponging miR-101-3p and activation of E2F8. J Cancer 2020;11(10):3002–3012; doi: 10.7150/jca.40592 Crossref, Medline, Google Scholar10. Zhao W, Fu H, Zhang S, et al. LncRNA SNHG16 drives proliferation, migration, and invasion of hemangioma endothelial cell through modulation of miR-520d-3p/STAT3 axis. Cancer Med-Us 2018;7(7):3311–3320; doi: 10.1002/cam4.1562 Crossref, Medline, Google Scholar11. Cai F, Jiang H, Li Y, et al. Upregulation of long non-coding RNA SNHG16 promotes diabetes-related RMEC dysfunction via activating NF-kappaB and PI3K/AKT pathways. Mol Ther Nucleic Acids 2021;24:512–527; doi: 10.1016/j.omtn.2021.01.035 Crossref, Medline, Google Scholar12. Zhang R, Ma X, Jiang L, et al. Decreased lncRNA SNHG16 accelerates oxidative stress induced pathological angiogenesis in human retinal microvascular endothelial cells by regulating miR-195/mfn2 Axis. Curr Pharm Des 2021;27(27):3047–3060; doi: 10.2174/1381612827666210202141541 Crossref, Medline, Google Scholar13. Atef MM, Shafik NM, Hafez YM, et al. The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: A cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway. Redox Rep 2022;27(1):70–78; doi: 10.1080/13510002.2022.2050086 Crossref, Medline, Google Scholar14. Zhao D, Zhao Y, Wang J, et al. Long noncoding RNA Hotair facilitates retinal endothelial cell dysfunction in diabetic retinopathy. Clin Sci (Lond) 2020;134(17):2419–2434; doi: 10.1042/CS20200694 Crossref, Medline, Google Scholar15. Biswas S, Feng B, Chen S, et al. The long non-coding RNA HOTAIR is a critical epigenetic mediator of angiogenesis in diabetic retinopathy. Invest Ophthalmol Vis Sci 2021;62(3):20; doi: 10.1167/iovs.62.3.20 Crossref, Medline, Google Scholar16. Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis 2014;5(10):e1506; doi: 10.1038/cddis.2014.466 Crossref, Medline, Google Scholar17. Yan B, Tao ZF, Li XM, et al. Aberrant expression of long noncoding RNAs in early diabetic retinopathy. Invest Ophthalmol Vis Sci 2014;55(2):941–951; doi: 10.1167/iovs.13–13221 Crossref, Medline, Google Scholar18. Xia F, Xu Y, Zhang X, et al. Competing endogenous RNA network associated with oxygen-induced retinopathy: Expression of the network and identification of the MALAT1/miR-124-3p/EGR1 regulatory axis. Exp Cell Res 2021;408(1):112783; doi: 10.1016/j.yexcr.2021.112783 Crossref, Medline, Google Scholar19. Yu L, Fu J, Yu N, et al. Long noncoding RNA MALAT1 participates in the pathological angiogenesis of diabetic retinopathy in an oxygen-induced retinopathy mouse model by sponging miR-203a-3p. Can J Physiol Pharmacol 2020;98(4):219–227; doi: 10.1139/cjpp-2019-0489 Crossref, Medline, Google Scholar20. Xu XD, Li KR, Li XM, et al. Long non-coding RNAs: New players in ocular neovascularization. Mol Biol Rep 2014;41(7):4493–4505; doi: 10.1007/s11033-014-3320-5 Crossref, Medline, Google Scholar21. Qiu GZ, Tian W, Fu HT, et al. Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. Biochem Biophys Res Commun 2016;471(1):135–141; doi: 10.1016/j.bbrc.2016.01.164 Crossref, Medline, Google Scholar22. Ruan W, Zhao F, Zhao S, et al. Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells. Gene 2018;649:32–39; doi: 10.1016/j.gene.2018.01.072 Crossref, Medline, Google Scholar23. Zhang D, Qin H, Leng Y, et al. LncRNA MEG3 overexpression inhibits the development of diabetic retinopathy by regulating TGF-β1 and VEGF. Exp Ther Med 2018;16(3):2337–2342; doi: 10.3892/etm.2018.6451 Crossref, Medline, Google Scholar24. Chen J, Liao L, Xu H, et al. Long non-coding RNA MEG3 inhibits neovascularization in diabetic retinopathy by regulating microRNA miR-6720-5p and cytochrome B5 reductase 2. Bioengineered 2021;12(2):11872–11884: doi: 10.1080/21655979.2021.2000721 Crossref, Google Scholar25. Shi L, Han X, Liu C, et al. Long non-coding RNA PNKY modulates the development of choroidal neovascularization. Front Cell Dev Biol 2022;10:836031; doi: 10.3389/fcell.2022.836031 Crossref, Medline, Google Scholar26. Zhou Q, Yu B, Anderson C, et al. LncEGFL7OS regulates human angiogenesis by interacting with MAX at the EGFL7/miR-126 locus. Elife 2019;8:e40470; doi: 10.7554/eLife.40470 Crossref, Medline, Google Scholar27. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384(5):403–416; doi: 10.1056/NEJMoa2035389 Crossref, Medline, Google Scholar28. Winkle M, El-Daly SM, Fabbri M, et al. Noncoding RNA therapeutics—Challenges and potential solutions. Nat Rev Drug Discov 2021;20(8):629–651; doi: 10.1038/s41573-021-00219-z Crossref, Medline, Google Scholar29. Qu L, Yi ZY, Shen Y, et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell 2022;185(10):1728–1744.e16; doi: 10.1016/j.cell.2022.03.044 Crossref, Medline, Google Scholar30. Abulwerdi FA, Xu W, Ageeli AA, et al. Selective small-molecule targeting of a triple helix encoded by the long noncoding RNA, MALAT1. ACS Chem Biol 2019;14(2):223–235; doi: 10.1021/acschembio.8b00807 Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Volume 39Issue 4May 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Shusheng Wang.Ribonucleic Acid (RNA) Therapeutics: Role of Long Noncoding RNAs in Ocular Vascular Diseases.Journal of Ocular Pharmacology and Therapeutics.May 2023.237-239.http://doi.org/10.1089/jop.2023.29104.editorialPublished in Volume: 39 Issue 4: May 10, 2023PDF download" @default.
• W4376270747 created "2023-05-13" @default.
• W4376270747 creator A5001097950 @default.
• W4376270747 date "2023-05-01" @default.
• W4376270747 modified "2023-10-18" @default.
• W4376270747 title "Ribonucleic Acid (RNA) Therapeutics: Role of Long Noncoding RNAs in Ocular Vascular Diseases" @default.
• W4376270747 cites W1994339101 @default.
• W4376270747 cites W2076873046 @default.
• W4376270747 cites W2151473756 @default.
• W4376270747 cites W2267388772 @default.
• W4376270747 cites W2594076864 @default.
• W4376270747 cites W2788022878 @default.
• W4376270747 cites W2806623877 @default.
• W4376270747 cites W2808173735 @default.
• W4376270747 cites W2884910822 @default.
• W4376270747 cites W2907733478 @default.
• W4376270747 cites W2910703604 @default.
• W4376270747 cites W2912244582 @default.
• W4376270747 cites W2985585531 @default.
• W4376270747 cites W2990373466 @default.
• W4376270747 cites W3006706038 @default.
• W4376270747 cites W3012791911 @default.
• W4376270747 cites W3076024347 @default.
• W4376270747 cites W3127564057 @default.
• W4376270747 cites W3128827265 @default.
• W4376270747 cites W3138712411 @default.
• W4376270747 cites W3171835979 @default.
• W4376270747 cites W3196753466 @default.
• W4376270747 cites W4200154610 @default.
• W4376270747 cites W4205483821 @default.
• W4376270747 cites W4212818649 @default.
• W4376270747 cites W4220949326 @default.
• W4376270747 cites W4220999759 @default.
• W4376270747 cites W4225656021 @default.
• W4376270747 cites W4226027283 @default.
• W4376270747 doi "https://doi.org/10.1089/jop.2023.29104.editorial" @default.
• W4376270747 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37172295" @default.
• W4376270747 hasPublicationYear "2023" @default.
• W4376270747 type Work @default.
• W4376270747 citedByCount "0" @default.
• W4376270747 crossrefType "journal-article" @default.
• W4376270747 hasAuthorship W4376270747A5001097950 @default.
• W4376270747 hasConcept C104317684 @default.
• W4376270747 hasConcept C145059251 @default.
• W4376270747 hasConcept C194993378 @default.
• W4376270747 hasConcept C54355233 @default.
• W4376270747 hasConcept C60644358 @default.
• W4376270747 hasConcept C62203573 @default.
• W4376270747 hasConcept C67705224 @default.
• W4376270747 hasConcept C70721500 @default.
• W4376270747 hasConcept C71924100 @default.
• W4376270747 hasConcept C86803240 @default.
• W4376270747 hasConceptScore W4376270747C104317684 @default.
• W4376270747 hasConceptScore W4376270747C145059251 @default.
• W4376270747 hasConceptScore W4376270747C194993378 @default.
• W4376270747 hasConceptScore W4376270747C54355233 @default.
• W4376270747 hasConceptScore W4376270747C60644358 @default.
• W4376270747 hasConceptScore W4376270747C62203573 @default.
• W4376270747 hasConceptScore W4376270747C67705224 @default.
• W4376270747 hasConceptScore W4376270747C70721500 @default.
• W4376270747 hasConceptScore W4376270747C71924100 @default.
• W4376270747 hasConceptScore W4376270747C86803240 @default.
• W4376270747 hasIssue "4" @default.
• W4376270747 hasLocation W43762707471 @default.
• W4376270747 hasLocation W43762707472 @default.
• W4376270747 hasOpenAccess W4376270747 @default.
• W4376270747 hasPrimaryLocation W43762707471 @default.
• W4376270747 hasRelatedWork W2031277122 @default.
• W4376270747 hasRelatedWork W2094292925 @default.
• W4376270747 hasRelatedWork W2123269114 @default.
• W4376270747 hasRelatedWork W2136288913 @default.
• W4376270747 hasRelatedWork W2217522595 @default.
• W4376270747 hasRelatedWork W3168777358 @default.
• W4376270747 hasRelatedWork W3194761285 @default.
• W4376270747 hasRelatedWork W4239958958 @default.
• W4376270747 hasRelatedWork W4285726509 @default.
• W4376270747 hasRelatedWork W2954286598 @default.
• W4376270747 hasVolume "39" @default.
• W4376270747 isParatext "false" @default.
• W4376270747 isRetracted "false" @default.
• W4376270747 workType "article" @default.