Tumor Biology

, Volume 37, Issue 7, pp 9527–9534 | Cite as

MicroRNAs modulating angiogenesis: miR-129-1 and miR-133 act as angio-miR in HUVECs

  • Mina Soufi-zomorrod
  • Abbas Hajifathali
  • Fatemeh Kouhkan
  • Mahshid Mehdizadeh
  • Seyed Mohammad Ali Hosseini Rad
  • Masoud Soleimani
Original Article


The sprouting of new blood vessels by angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to enormous pathological conditions such as ischemia and cancer. MicroRNAs (also known as miRNAs or miRs) play key roles in regulation of a range of cellular processes by posttranscriptional suppression of their target genes. Recently, new studies have indicated that miRNAs are involved in certain angiogenic settings and signaling pathways use these non-coding RNAs to promote or suppress angiogenic processes. Herein, VEGFR2 and FGFR1 were identified as miR-129-1 and miR-133 targets using bioinformatic algorithms, respectively. Afterwards, using luciferase reporter assay and gene expression analysis at both mRNA and protein levels, VEGFR2 and FGFR1 were validated as miR-129-1 and miR-133 targets. In addition, we showed that miR-129-1 and miR-133 suppress angiogenesis properties such as proliferation rate, cell viability, and migration activity of human umbilical vein endothelial cells (HUVEC) in vitro. We conclude that these miRNAs can suppress key factors of angiogenesis by directly targeting them. These results have important therapeutic implications for a variety of diseases involving deregulation of angiogenesis, including cancer.


MiR-129-1 MiR-133 Angiogenesis VEGFR2 FGFR1 HUVEC cells 



This project has been funded by Tarbiat Modares University and Stem Cell Technology Research Center, Tehran, Iran. The authors also thank Arash Veshkini for assistance in preparing the Figures.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Ichihara E, Kiura K, Tanimoto M. Targeting angiogenesis in cancer therapy. Acta Med Okayama. 2011;65(6):353–62.PubMedGoogle Scholar
  2. 2.
    Rivera LB, Bergers G. CANCER. Tumor angiogenesis, from foe to friend. Science. 2015;349(6249):694–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Sakurai T, Kudo M. Signaling pathways governing tumor angiogenesis. Oncology. 2011;81(1):24–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Tonini T, Rossi F, Claudio PP. Molecular basis of angiogenesis and cancer. Oncogene. 2003;22(42):6549–56.CrossRefPubMedGoogle Scholar
  5. 5.
    Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol. 2006;7(5):359–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Presta M, Dell'Era P, Mitola S, Moroni E, Ronca R, Rusnati M. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16(2):159–78.CrossRefPubMedGoogle Scholar
  7. 7.
    Rad SM, Langroudi L, Kouhkan F, Yazdani L, Koupaee AN, Asgharpour S, et al. Transcription factor decoy: a pre-transcriptional approach for gene downregulation purpose in cancer. Tumour Biol. 2015;36(7):4871–81.CrossRefPubMedGoogle Scholar
  8. 8.
    Dyrskjot L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R, et al. Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res. 2009;69(11):4851–60.CrossRefPubMedGoogle Scholar
  9. 9.
    Tsai KW, Wu CW, Hu LY, Li SC, Liao YL, Lai CH, et al. Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. Int J Cancer. 2011;129(11):2600–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38(2):228–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Heusschen R, van Gink M, Griffioen AW, Thijssen VL. MicroRNAs in the tumor endothelium: novel controls on the angioregulatory switchboard. Biochim Biophys Acta. 2010;1805(1):87–96.PubMedGoogle Scholar
  12. 12.
    Liu Y, Wang W, Wang J, Wang Y, Yuan Z, Tang S, et al. Blood compatibility evaluation of poly(D,L-lactide-co-beta-malic acid) modified with the GRGDS sequence. Colloids Surf B Biointerfaces. 2010;75(1):370–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Li YX, Liu DQ, Zheng C, Zheng SQ, Liu M, Li X, et al. miR-200a modulate HUVECs viability and migration. IUBMB Life. 2011;63(7):553–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, et al. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008;14(5):382–93.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Suarez Y, Sessa WC. MicroRNAs as novel regulators of angiogenesis. Circ Res. 2009;10(4):442–54.CrossRefGoogle Scholar
  16. 16.
    Fish JE, Srivastava D. MicroRNAs: opening a new vein in angiogenesis research. Sci Signal. 2009;2(52):pe1.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wu J, Qian J, Li C, Kwok L, Cheng F, Liu P, et al. miR-129 regulates cell proliferation by downregulating Cdk6 expression. Cell Cycle. 2010;9(9):1809–18.CrossRefPubMedGoogle Scholar
  18. 18.
    Karaayvaz M, Zhai H, Ju J. miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer. Cell Death Dis. 2013;4:e659.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol. 2007;23:175–205.CrossRefPubMedGoogle Scholar
  20. 20.
    Chamorro-Jorganes A, Araldi E, Penalva LO, Sandhu D, Fernández-Hernando C, Suárez Y. MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arterioscler Thromb Vasc Biol. 2011;31(11):2595–606.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Mina Soufi-zomorrod
    • 1
  • Abbas Hajifathali
    • 2
  • Fatemeh Kouhkan
    • 3
  • Mahshid Mehdizadeh
    • 4
  • Seyed Mohammad Ali Hosseini Rad
    • 3
  • Masoud Soleimani
    • 1
  1. 1.Department of Hematology, School of Medical SciencesTerbiat Modares UniversityTehranIran
  2. 2.Department of Medical GeneticsShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Stem Cell Technology Research CenterTehranIran
  4. 4.Shahid Beheshti University of Medical ScienceTehranIran

Personalised recommendations