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Regulation of vascular endothelial growth factor signaling by miR-200b

  • Published:
Molecules and Cells

Abstract

Vascular endothelial growth factor (VEGF) signaling plays an important role in angiogenesis. In the VEGF signaling pathway, the key components are VEGF and its receptors, Flt-1 and KDR. In this study, we show that transfection of synthetic miR-200b reduced protein levels of VEGF, Flt-1, and KDR. In A549 cells, miR-200b targeted the predicted binding sites in the 3′-untranslated region (3′-UTR) of VEGF, Flt-1, and KDR as revealed by a luciferase reporter assay. When transfected with miR-200b, the ability of HUVECs to form a capillary tube on Matrigel and VEGF-induced phosphorylation of ERK1/2 were significantly reduced. Taken together, these results suggest that miR-200b negatively regulates VEGF signaling by targeting VEGF and its receptors and that miR-200b may have therapeutic potential as an angiogenesis inhibitor.

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References

  • Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297.

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet, P. (2005). Angiogenesis in life, disease and medicine. Nature 438, 932–936.

    Article  PubMed  CAS  Google Scholar 

  • Chan, Y.C., Khanna, S., Roy, S., and Sen, C.K. (2011). miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J. Biol. Chem. 286, 2047–2056.

    Article  PubMed  CAS  Google Scholar 

  • Eskens, F.A. (2004). Angiogenesis inhibitors in clinical development; where are we now and where are we going? Br. J. Cancer 90, 1–7.

    Article  PubMed  CAS  Google Scholar 

  • Ferrara, N. (1999). Molecular and biological properties of vascular endothelial growth factor. J. Mol. Med. 77, 527–543.

    Article  PubMed  CAS  Google Scholar 

  • Ferrara, N. (2004). Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 25, 581–611.

    Article  PubMed  CAS  Google Scholar 

  • Ferrara, N., and Kerbel, R.S. (2005). Angiogenesis as a therapeutic target. Nature 438, 967–974.

    Article  PubMed  CAS  Google Scholar 

  • Ferrara, N., Gerber, H.P., and LeCouter, J. (2003). The biology of VEGF and its receptors. Nat. Med. 9, 669–676.

    Article  PubMed  CAS  Google Scholar 

  • Fish, J.E., Santoro, M.M., Morton, S.U., Yu, S., Yeh, R.F., Wythe, J.D., Ivey, K.N., Bruneau, B.G., Stainier, D.Y., and Srivastava, D. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Dev. Cell 15, 272–284.

    Article  PubMed  CAS  Google Scholar 

  • Folkman, J. (1971). Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186.

    Article  PubMed  CAS  Google Scholar 

  • Folkman, J. (1995). Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1, 27–31.

    Article  PubMed  CAS  Google Scholar 

  • Graff, J.R., Herman, J.G., Lapidus, R.G., Chopra, H., Xu, R., Jarrard, D.F., Isaacs, W.B., Pitha, P.M., Davidson, N.E., and Baylin, S.B. (1995). E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 55, 5195–5199.

    PubMed  CAS  Google Scholar 

  • Gregory, P.A., Bert, A.G., Paterson, E.L., Barry, S.C., Tsykin, A., Farshid, G., Vadas, M.A., Khew-Goodall, Y., and Goodall, G.J. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat. Cell Biol. 10, 593–601.

    Article  PubMed  CAS  Google Scholar 

  • He, L., and Hannon, G.J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5, 522–531.

    Article  PubMed  CAS  Google Scholar 

  • Hua, Z., Lv, Q., Ye, W., Wong, C.K., Cai, G., Gu, D., Ji, Y., Zhao, C., Wang, J., Yang, B.B., et al. (2006). MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1, e116.

    Article  PubMed  Google Scholar 

  • Kim, V.N. (2005). Small RNAs: classification, biogenesis, and function. Mol. Cells 19, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Kim, S., Lee, U.J., Kim, M.N., Lee, E.J., Kim, J.Y., Lee, M.Y., Choung, S., Kim, Y.J., and Choi, Y.C. (2008). MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J. Biol. Chem. 283, 18158–18166.

    Article  PubMed  CAS  Google Scholar 

  • Liu, H., Brannon, A.R., Reddy, A.R., Alexe, G., Seiler, M.W., Arreola, A., Oza, J.H., Yao, M., Juan, D., Liou, L.S., et al. (2010). Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell renal cell carcinoma. BMC Syst. Biol. 4, 51.

    Article  PubMed  Google Scholar 

  • Park, S.M., Gaur, A.B., Lengyel, E., and Peter, M.E. (2008). The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22, 894–907.

    Article  PubMed  CAS  Google Scholar 

  • Roybal, J.D., Zang, Y., Ahn, Y.H., Yang, Y., Gibbons, D.L., Baird, B.N., Alvarez, C.A., Thilaganathan, N., Saintigny, P., Liu, D., et al. (2011). miR-200 inhibits lung adenocarcinoma cell invasion and metastasis by targeting Flt1/VEGFR1. Mol. Cancer Res. 9, 25–35.

    Article  PubMed  CAS  Google Scholar 

  • Suárez, Y., and Sessa, W.C. (2009). MicroRNAs as novel regulators of angiogenesis. Circ. Res. 104, 442–454.

    Article  PubMed  Google Scholar 

  • van Solingen, C., Seghers, L., Bijkerk, R., Duijs, J.M., Roeten, M.K., van Oeveren-Rietdijk, A.M., Baelde, H.J., Monge, M., Vos, J.B., de Boer, H.C., et al. (2009). Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J. Cell. Mol. Med. 13, 1577–1585.

    Article  PubMed  Google Scholar 

  • Vrba, L., Jensen, T.J., Garbe, J.C., Heimark, R.L., Cress, A.E., Dickinson, S., Stampfer, M.R., and Futscher, B.W. (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One 5, e8697.

    Article  PubMed  Google Scholar 

  • Wang, S., and Olson, E.N. (2009). AngiomiRs—key regulators of angiogenesis. Curr. Opin. Genet. Dev. 19, 205–211.

    Article  PubMed  CAS  Google Scholar 

  • Wang, S., Aurora, A.B., Johnson, B.A., Qi, X., McAnally, J., Hill, J.A., Richardson, J.A., Bassel-Duby, R., and Olson, E.N. (2008). The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev. Cell 15, 261–271.

    Article  PubMed  Google Scholar 

  • Wiklund, E.D., Bramsen, J.B., Hulf, T., Dyrskjøt, L., Ramanathan, R., Hansen, T.B., Villadsen, S.B., Gao, S., Ostenfeld, M.S., Borre, M., et al. (2010). Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int. J. Cancer 128, 1327–1334.

    Article  Google Scholar 

  • Wu, F., Yang, Z., and Li, G. (2009). Role of specific microRNAs for endothelial function and angiogenesis. Biochem. Biophys. Res. Commun. 386, 549–553.

    Article  PubMed  CAS  Google Scholar 

  • Yoshiura, K., Kanai, Y., Ochiai, A., Shimoyama, Y., Sugimura, T., and Hirohashi, S. (1995). Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc. Natl. Acad. Sci. USA 92, 7416–7419.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Kwanghee Baek.

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These authors contributed equally to this work.

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Choi, YC., Yoon, S., Jeong, Y. et al. Regulation of vascular endothelial growth factor signaling by miR-200b. Mol Cells 32, 77–82 (2011). https://doi.org/10.1007/s10059-011-1042-2

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  • DOI: https://doi.org/10.1007/s10059-011-1042-2

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