Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2020 Volume 21 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2020 Volume 21 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions

  • Authors:
    • Xiaoxue Zhao
    • Xiufang Wei
    • Xueying Wang
    • Guoxian Qi
  • View Affiliations / Copyright

    Affiliations: Department of Geriatrics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2560-2570
    |
    Published online on: April 8, 2020
       https://doi.org/10.3892/mmr.2020.11064
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Dysregulation of angiogenesis can be caused by hypoxia, which may result in severe diseases of the heart, including coronary artery disease. Hypoxia‑inducible factor 1 (HIF‑1) modulates angiogenesis via the regulation of several angiogenic factors. However, the underlying mechanism of hypoxia‑induced angiogenesis remains unknown. In the present study, it was hypothesized that long non‑coding RNA (lncRNA) non‑coding RNA activated by DNA damage (NORAD) may serve a role in the process of angiogenesis via the regulation of microRNA(miR)‑590‑3p under hypoxic conditions. The effect of NORAD and miR‑590‑3p on cell viability and properties associated with angiogenesis, including cell migration and tube formation in human umbilical vein endothelial cells (HUVECs) under hypoxic conditions, were assessed. Potential downstream angiogenic factors of miR‑590‑3p were also determined by molecular experiments. It was identified that NORAD expression was upregulated and miR‑590‑3p expression was downregulated in hypoxia‑exposed HUVECs, and also in myocardial infarction (MI) left ventricle tissues in mice. Moreover, downregulation of NORAD expression resulted in decreased cell viability and angiogenic capacity, but further knocking down miR‑590‑3p expression reversed these alterations, resulting in increased cell migration and tube formation in HUVECs under hypoxic conditions for 24 h. It was demonstrated that NORAD overexpression also increased cell vitality and tube‑formation capacity. Furthermore, NORAD was identified to bind with miR‑590‑3p directly, and miR‑590‑3p was shown to target certain proangiogenic agents, such as vascular endothelial growth factor (VEGF)A, fibroblast growth factor (FGF)1 and FGF2 directly. Therefore, the present results suggested that lncRNA NORAD may bind with miR‑590‑3p to regulate the angiogenic ability of HUVECs via the regulation of several downstream proangiogenic factors under hypoxia. Thus, the lncRNA NORAD/miR‑590‑3p axis may be a novel regulatory pathway in the angiogenic mechanisms in HUVECs, which highlights a potentially novel perspective for treating ischemia/hypoxia‑induced angiogenic diseases.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med. 6:389–395. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Risau W: Mechanisms of angiogenesis. Nature. 386:671–674. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ and Holash J: Vascular-specific growth factors and blood vessel formation. Nature. 407:242–248. 2000. View Article : Google Scholar : PubMed/NCBI

4 

Ferrara N: Vascular endothelial growth factor: Molecular and biological aspects. Curr Top Microbiol Immunol. 237:1–30. 1999.PubMed/NCBI

5 

Zimna A and Kurpisz M: Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis: Applications and therapies. Biomed Res Int. 2015:5494122015. View Article : Google Scholar : PubMed/NCBI

6 

Greijer AE, van der Groep P, Kemming D, Shvarts A, Semenza GL, Meijer GA, van de Wiel MA, Belien JA, van Diest PJ and van der Wall E: Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1). J Pathol. 206:291–304. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Semenza GL: Angiogenesis in ischemic and neoplastic disorders. Annu Rev Med. 54:17–28. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Mori S, Tran V, Nishikawa K, Kaneda T, Hamada Y, Kawaguchi N, Fujita M, Saegusa J, Takada YK, Matsuura N, et al: A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis. PLoS One. 8:e579272013. View Article : Google Scholar : PubMed/NCBI

9 

Semenza GL: Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol. 9:47–71. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, et al: Heart disease and stroke statistics-2013 update: A report from the American heart association. Circulation. 127:e6–e245. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Murray CJ and Lopez AD: Mortality by cause for eight regions of the world: Global burden of disease study. Lancet. 349:1269–1276. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Lavine KJ, Kovacs A, Weinheimer C and Mann DL: Repetitive myocardial ischemia promotes coronary growth in the adult mammalian heart. J Am Heart Assoc. 2:e0003432013. View Article : Google Scholar : PubMed/NCBI

13 

Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Kung JT, Colognori D and Lee JT: Long noncoding RNAs: Past, present, and future. Genetics. 193:651–669. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Han P, Li W, Lin CH, Yang J, Shang C, Nuernberg ST, Jin KK, Xu W, Lin CY, Lin CJ, et al: A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 514:102–106. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Wang K, Long B, Zhou LY, Liu F, Zhou QY, Liu CY, Fan YY and Li PF: CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun. 5:35962014. View Article : Google Scholar : PubMed/NCBI

17 

Lee S, Kopp F, Chang TC, Sataluri A, Chen B, Sivakumar S, Yu H, Xie Y and Mendell JT: Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell. 164:69–80. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Liu H, Li J, Koirala P, Ding X, Chen B, Wang Y, Wang Z, Wang C, Zhang X and Mo YY: Long non-coding RNAs as prognostic markers in human breast cancer. Oncotarget. 7:20584–20596. 2016.PubMed/NCBI

19 

Li H, Wang X, Wen C, Huo Z, Wang W, Zhan Q, Cheng D, Chen H, Deng X, Peng C and Shen B: Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer. Mol Cancer. 16:1692017. View Article : Google Scholar : PubMed/NCBI

20 

Miao Z, Guo X and Tian L: The long noncoding RNA NORAD promotes the growth of gastric cancer cells by sponging miR-608. Gene. 687:116–124. 2019. View Article : Google Scholar : PubMed/NCBI

21 

Kawasaki N, Miwa T, Hokari S, Sakurai T, Ohmori K, Miyauchi K, Miyazono K and Koinuma D: Long noncoding RNA NORAD regulates transforming growth factor-β signaling and epithelial-to-mesenchymal transition-like phenotype. Cancer Sci. 109:2211–2220. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Ekhteraei-Tousi S, Mohammad-Soltani B, Sadeghizadeh M, Mowla SJ, Parsi S and Soleimani M: Inhibitory effect of hsa-miR-590-5p on cardiosphere-derived stem cells differentiation through downregulation of TGFβ signaling. J Cell Biochem. 116:179–191. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Jafarzadeh M and Soltani BM: Hsa-miR-590-5p interaction with SMAD3 transcript supports its regulatory effect on The TGFβ signaling pathway. Cell J. 18:7–12. 2016.PubMed/NCBI

24 

Nallamshetty S, Chan SY and Loscalzo J: Hypoxia: A master regulator of microRNA biogenesis and activity. Free Radic Biol Med. 64:20–30. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Kumar MM and Goyal R: LncRNA as a therapeutic target for angiogenesis. Curr Top Med Chem. 17:1750–1757. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Rehmsmeier M, Steffen P, Hochsmann M and Giegerich R: Fast and effective prediction of microRNA/target duplexes. RNA. 10:1507–1517. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Guide for the Care and Use of Laboratory Animals. Institute for Laboratory Animal Research. National Academies Press. (Washington, DC). 2011.

29 

Yang Z, Zhao Y, Lin G, Zhou X, Jiang X and Zhao H: Noncoding RNA activated by DNA damage (NORAD): Biologic function and mechanisms in human cancers. Clin Chim Acta. 489:5–9. 2019. View Article : Google Scholar : PubMed/NCBI

30 

Madanecki P, Kapoor N, Bebok Z, Ochocka R, Collawn JF and Bartoszewski R: Regulation of angiogenesis by hypoxia: The role of microRNA. Cell Mol Biol Lett. 18:47–57. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Folkman J and Shing Y: Angiogenesis. J Biol Chem. 267:10931–10934. 1992.PubMed/NCBI

32 

Geng L, Chaudhuri A, Talmon G, Wisecarver JL and Wang J: TGF-Beta suppresses VEGFA-mediated angiogenesis in colon cancer metastasis. PLoS One. 8:e599182013. View Article : Google Scholar : PubMed/NCBI

33 

Aplin AC and Nicosia RF: Hypoxia paradoxically inhibits the angiogenic response of isolated vessel explants while inducing overexpression of vascular endothelial growth factor. Angiogenesis. 19:133–146. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Noren Hooten N, Abdelmohsen K, Gorospe M, Ejiogu N, Zonderman AB and Evans MK: microRNA expression patterns reveal differential expression of target genes with age. PLoS One. 5:e107242010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao X, Wei X, Wang X and Qi G: Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions. Mol Med Rep 21: 2560-2570, 2020.
APA
Zhao, X., Wei, X., Wang, X., & Qi, G. (2020). Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions. Molecular Medicine Reports, 21, 2560-2570. https://doi.org/10.3892/mmr.2020.11064
MLA
Zhao, X., Wei, X., Wang, X., Qi, G."Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions". Molecular Medicine Reports 21.6 (2020): 2560-2570.
Chicago
Zhao, X., Wei, X., Wang, X., Qi, G."Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions". Molecular Medicine Reports 21, no. 6 (2020): 2560-2570. https://doi.org/10.3892/mmr.2020.11064
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao X, Wei X, Wang X and Qi G: Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions. Mol Med Rep 21: 2560-2570, 2020.
APA
Zhao, X., Wei, X., Wang, X., & Qi, G. (2020). Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions. Molecular Medicine Reports, 21, 2560-2570. https://doi.org/10.3892/mmr.2020.11064
MLA
Zhao, X., Wei, X., Wang, X., Qi, G."Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions". Molecular Medicine Reports 21.6 (2020): 2560-2570.
Chicago
Zhao, X., Wei, X., Wang, X., Qi, G."Long non‑coding RNA NORAD regulates angiogenesis of human umbilical vein endothelial cells via miR‑590‑3p under hypoxic conditions". Molecular Medicine Reports 21, no. 6 (2020): 2560-2570. https://doi.org/10.3892/mmr.2020.11064
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team