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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October-2017 Volume 14 Issue 4

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
October-2017 Volume 14 Issue 4

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

MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1

  • Authors:
    • Shifeng Fang
    • Xiang Ma
    • Suping Guo
    • Jianmin Lu
  • View Affiliations / Copyright

    Affiliations: Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
  • Pages: 4311-4318
    |
    Published online on: August 1, 2017
       https://doi.org/10.3892/ol.2017.6695
  • 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

Diabetic retinopathy (DR) is a sight-threatening complication of diabetes. IRS‑1 was predicted to be the target gene of microRNA‑126 (miR‑126). The present study was designed to illustrate the involvement of miR‑126 in the regulation of DR via targeting IRS‑1. The present study revealed that the expression of miR‑126 was significantly decreased while IRS‑1 expression was increased in endothelial cells (ECs) and retinal pericytes (RPs) from a DR mouse model compared with healthy controls. Furthermore, a luciferase reporter assay confirmed the interaction between miR‑126 and IRS‑1. Following transfection with anmiR‑126 mimic or miR‑126 inhibitor, overexpression of miR‑126 was demonstrated to suppress the invasion and viability of ECs and RPs and to inhibit the IRS‑1 and phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway protein expression levels, with inhibition of miR‑126 leading to reverse results. Furthermore, transfection with small interfering RNA targeting IRS‑1 altered the miR‑126‑induced effects observed in ECs, indicating that miR‑126 may suppress angiogenesis in DR via inhibition ofIRS‑1 expression. Taken together, the results of the present study suggested that miR‑126 affected the expression of IRS‑1, resulting in downregulated expression of PI3K/Akt pathway proteins, and also suppressed cell invasion and viability. These results may provide a potential therapeutic strategy for DR.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Congdon NG, Friedman DS and Lietman T: Important causes of visual impairment in the world today. JAMA. 290:2057–2060. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Armulik A, Abramsson A and Betsholtz C: Endothelial/pericyte interactions. Circ Res. 97:512–523. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH and Caldwell RW: Vascular endothelial growth factor and diabetic retinopathy: Pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev. 19:442–455. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Saltiel AR and Pessin JE: Insulin signaling pathways in time and space. Trends Cell Biol. 12:65–71. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Ferrara N: Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 280:C1358–C1366. 2001.PubMed/NCBI

6 

Behl T and Kotwani A: Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy. Pharmacol Res. 99:137–148. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Poulaki V, Qin W, Joussen AM, Hurlbut P, Wiegand SJ, Rudge J, Yancopoulos GD and Adamis AP: Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. J Clin Invest. 109:805–815. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Jiang ZY, He Z, King BL, Kuroki T, Opland DM, Suzuma K, Suzuma I, Ueki K, Kulkarni RN, Kahn CR and King GL: Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesis. J Biol Chem. 278:31964–31971. 2003. View Article : Google Scholar : PubMed/NCBI

9 

American Diabetes Association, . Peripheral arterial disease in people with diabetes. Diabetes Care. 26:3333–3341. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Waltenberger J: Impaired collateral vessel development in diabetes: Potential cellular mechanisms and therapeutic implications. Cardiovasc Res. 49:554–560. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Carlsson PO and Jansson L: Disruption of insulin receptor signaling in endothelial cells shows the central role of an intact islet blood flow for in vivo β-cell function. Diabetes. 64:700–702. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Tardif K, Hertig V, Dumais C, Villeneuve L, Perrault L, Tanguay JF and Calderone A: Nestin downregulation in rat vascular smooth muscle cells represents an early marker of vascular disease in experimental type I diabetes. Cardiovasc Diabetol. 13:1192014. View Article : Google Scholar : PubMed/NCBI

13 

Park SW, Yun JH and Kim JH, Kim KW, Cho CH and Kim JH: Angiopoietin 2 induces pericyte apoptosis via α3β1 integrin signaling in diabetic retinopathy. Diabetes. 63:3057–3068. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF and King GL: Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J Clin Invest. 104:447–457. 1999. View Article : Google Scholar : PubMed/NCBI

15 

Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Zhang J, Du YY, Lin YF, Chen YT, Yang L, Wang HJ and Ma D: The cell growth suppressor, mir-126, targets IRS-1. Biochem Biophys Res Commun. 377:136–140. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Figliolini F, Cantaluppi V, De Lena M, Beltramo S, Romagnoli R, Salizzoni M, Melzi R, Nano R, Piemonti L, Tetta C, et al: Isolation, characterization and potential role in beta cell-endothelium cross-talk of extracellular vesicles released from human pancreatic islets. PLoS One. 9:e1025212014. View Article : Google Scholar : PubMed/NCBI

18 

Bandello F, Lattanzio R, Zucchiatti I and Del Turco C: Pathophysiology and treatment of diabetic retinopathy. Acta Diabetol. 50:1–20. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Liang D, Zhong P, Hu J, Lin F, Qian Y, Xu Z, Wang J, Zeng C, Li X and Liang G: EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stressin STZ-induced diabetic mouse model. J Mol Cell Cardiol. 82:63–74. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Su X, Sorenson CM and Sheibani N: Isolation and characterization of murine retinal endothelial cells. Mol Vis. 9:171–178. 2003.PubMed/NCBI

21 

Buzney SM, Massicotte SJ, Hetu N and Zetter BR: Retinal vascular endothelial cells and pericytes. Differential growth characteristics in vitro. Invest Ophthalmol Vis Sci. 24:470–480. 1983.PubMed/NCBI

22 

Meng S, Cao JT, Zhang B, Zhou Q, Shen CX and Wang CQ: Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol. 53:64–72. 2012. View Article : Google Scholar : PubMed/NCBI

23 

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

24 

Zhang J, Du YY, Lin YF, Chen YT, Yang L, Wang HJ and Ma D: The cell growth suppressor, mir-126, targets IRS-1. Biochem Biophys Res Commun. 377:136–140. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Cesarone G, Garofalo C, Abrams MT, Igoucheva O, Alexeev V, Yoon K, Surmacz E and Wickstrom E: RNAi-mediated silencing of insulin receptor substrate 1 (IRS-1) enhances tamoxifen-induced cell death in MCF-7 breast cancer cells. J Cell Biochem. 98:440–450. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of humangenes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Hoeppner LH, Sinha S, Wang Y, Bhattacharya R, Dutta S, Gong X, Bedell VM, Suresh S, Chun C, Ramchandran R, et al: RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells. J Cell Sci. 128:3556–3568. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Simó R, Sundstrom JM and Antonetti DA: Ocular anti-VEGF therapy for diabetic retinopathy: The role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care. 37:893–899. 2014. View Article : Google Scholar : PubMed/NCBI

29 

King GL, Goodman AD, Buzney S, Moses A and Kahn CR: Receptors and growth-promoting effects of insulin and insulinlike growth factors on cells from bovine retinal capillaries and aorta. J Clin Invest. 75:1028–1036. 1985. View Article : Google Scholar : PubMed/NCBI

30 

Kerouz NJ, Hörsch D, Pons S and Kahn CR: Differential regulation of insulin receptor substrates-1 and-2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest. 100:3164–3172. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Ryu HS, Park SY, Ma D, Zhang J and Lee W: The induction of microRNA targeting IRS-1 is involved in the development of insulin resistance under conditions of mitochondrial dysfunction in hepatocytes. PLoS One. 6:e173432011. View Article : Google Scholar : PubMed/NCBI

32 

Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R and Olson EN: The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 15:261–271. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Shibuya M and Claesson-Welsh L: Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 312:549–560. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Kanehisa M, Furumichi M, Tanabe M, Sato Y and Morishima K: KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45:D353–D361. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Fang S, Ma X, Guo S and Lu J: MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1. Oncol Lett 14: 4311-4318, 2017.
APA
Fang, S., Ma, X., Guo, S., & Lu, J. (2017). MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1. Oncology Letters, 14, 4311-4318. https://doi.org/10.3892/ol.2017.6695
MLA
Fang, S., Ma, X., Guo, S., Lu, J."MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1". Oncology Letters 14.4 (2017): 4311-4318.
Chicago
Fang, S., Ma, X., Guo, S., Lu, J."MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1". Oncology Letters 14, no. 4 (2017): 4311-4318. https://doi.org/10.3892/ol.2017.6695
Copy and paste a formatted citation
x
Spandidos Publications style
Fang S, Ma X, Guo S and Lu J: MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1. Oncol Lett 14: 4311-4318, 2017.
APA
Fang, S., Ma, X., Guo, S., & Lu, J. (2017). MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1. Oncology Letters, 14, 4311-4318. https://doi.org/10.3892/ol.2017.6695
MLA
Fang, S., Ma, X., Guo, S., Lu, J."MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1". Oncology Letters 14.4 (2017): 4311-4318.
Chicago
Fang, S., Ma, X., Guo, S., Lu, J."MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1". Oncology Letters 14, no. 4 (2017): 4311-4318. https://doi.org/10.3892/ol.2017.6695
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