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Noncoding RNAs in Tumor Angiogenesis

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The Long and Short Non-coding RNAs in Cancer Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 927))

Abstract

Solid tumors require angiogenesis to grow beyond 2 mm in size. In most cases, tumor cells undergo angiogenic switch and secrete substances that are required for generation of new capillary sprouting from existing blood vessels. Tumor angiogenesis is driven by a complex interplay between pro-angiogenic (VEGF/VEGFR, PDGF/PDGFR) and anti-angiogenic factors (TSP-1/TSP-2) within the tumor microenvironment. In addition, control of tissue remodeling and degradation by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) contribute to tumor angiogenesis. Furthermore, tumor suppressors or oncogenes that control cellular motility and maintain or promote hypoxia (HIFs and MYC) are also actively playing roles in tumor angiogenesis. Noncoding RNAs (ncRNAs), including microRNAs, are a novel class of regulatory molecules that control the gene expression in a posttranscriptional manner. MicroRNAs regulate important physiological processes, such as proliferation, apoptosis, and differentiation, as well as pathological conditions including oncogenesis. Accumulating evidence suggests that microRNAs directly modulate the process of angiogenesis by targeting important angiogenic factors and signaling molecules. Understanding the molecular mechanism behind the regulation of angiogenesis by microRNAs is important due to their therapeutic potential which may lead to improving outcome for cancer patients. Besides, ncRNAs with a regulatory role in angiogenesis, such as long noncoding RNAs (lncRNAs), have been identified in the genome. However, the mechanisms of the vast majority of lncRNAs are currently unknown. For the few lncRNAs characterized at the functional level, accumulating evidence shows that they play important roles in malignant diseases. The function and mechanism in angiogenesis will be described in this chapter.

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References

  1. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438(7070):932–6.

    Article  CAS  PubMed  Google Scholar 

  2. Carmeliet P, Peter C. Angiogenesis in health and disease. Nat Med. 2003;9(6):653–60.

    Article  CAS  PubMed  Google Scholar 

  3. Yancopoulos GD, et al. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407(6801):242–8.

    Article  CAS  PubMed  Google Scholar 

  4. Hanahan D, Douglas H, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

    Article  CAS  PubMed  Google Scholar 

  5. Folkman J, Judah F. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1(1):27–30.

    Article  CAS  PubMed  Google Scholar 

  6. Zheng PS, Wen J, Ang LC, et al. Versican/PG-M G3 domain promotes tumor growth and angiogenesis. FASEB J. 2004;18(6):754–6.

    CAS  PubMed  Google Scholar 

  7. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86(3):353–64.

    Article  CAS  PubMed  Google Scholar 

  8. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6(4):389–95.

    Article  CAS  PubMed  Google Scholar 

  9. Folkman J, Judah F. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29(6Q):15–8.

    Article  CAS  PubMed  Google Scholar 

  10. Dalmay T, Edwards DR. MicroRNAs and the hallmarks of cancer. Oncogene. 2006;25(46):6170–5.

    Article  CAS  PubMed  Google Scholar 

  11. Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med. 2009;60(1):167–79.

    Article  CAS  PubMed  Google Scholar 

  12. Lee YS, Anindya D. MicroRNAs in cancer. Annu Rev Pathol. 2009;4(1):199–227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  CAS  PubMed  Google Scholar 

  14. Graves P, Zeng Y. Biogenesis of mammalian microRNAs: a global view. Genomics Proteomics Bioinformatics. 2012;10(5):239–45.

    Article  CAS  PubMed  Google Scholar 

  15. Yang WJ, Yang DD, Songqing N, et al. Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem. 2005;280(10):9330–5.

    Article  CAS  PubMed  Google Scholar 

  16. Otsuka M, Zheng M, Hayashi M, et al. Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest. 2008;118(5):1944–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Giraldez AJ, Cinalli RM, Glasner ME, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005;308(5723):833–8.

    Article  CAS  PubMed  Google Scholar 

  18. Suárez Y, Fernández-Hernando C, Pober JS, et al. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007;100(8):1164–73.

    Article  PubMed  CAS  Google Scholar 

  19. Kuehbacher A, Urbich C, Zeiher AM, et al. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res. 2007;101(1):59–68.

    Article  CAS  PubMed  Google Scholar 

  20. Shilo S, Roy S, Khanna S, et al. Evidence for the involvement of miRNA in redox regulated angiogenic response of human microvascular endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28(3):471–7.

    Article  CAS  PubMed  Google Scholar 

  21. Graham RJ, Jan CH, Bartel DP, et al. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448(7149):83–6.

    Article  CAS  Google Scholar 

  22. Barik S, Sailen B, Titus B. Intronic microRNA: creation, evolution and regulation. In: Gusev Y, editor. MicroRNA profiling in cancer: a bioinformatics perspective. Singapore: Pan Stanford; 2009. p. 117–31.

    Chapter  Google Scholar 

  23. Okamura K, Hagen JW, Hong D, et al. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell. 2007;130(1):89–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pushpavalli SN, Bag I, Pal-Bhadra M, et al. Drosophila Argonaute-1 is critical for transcriptional cosuppression and heterochromatin formation. Chromosome Res. 2012;20(3):333–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fukagawa T, Nogami M, Yoshikawa M, et al. Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat Cell Biol. 2004;6(8):784–91.

    Article  CAS  PubMed  Google Scholar 

  26. Poliseno L, Tuccoli A, Mariani L, et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood. 2006;108(9):3068–71.

    Article  CAS  PubMed  Google Scholar 

  27. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435(7043):828–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dews M, Homayouni A, Yu D, et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet. 2006;38(9):1060–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Suárez Y, Fernandez-Hernando C, Yu J, et al. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci U S A. 2008;105(37):14082–7.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Khorshidi A, Dhaliwal P, Yang BB. Anti-tumor activity of miR-17 in melanoma. Cell Cycle. 2015;14(16):2549–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li H, Gupta S, Du WW, et al. MicroRNA-17 inhibits tumor growth by stimulating T-cell mediated host immune response. Oncoscience. 2014;1(7):531–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Fang L, Li H, Wang L, et al. MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget. 2014;5(10):2974–87.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Li H, Yang BB. MicroRNA-regulated stress response in cancer and its clinical implications. Cell Cycle. 2013;12(13):1983–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shan SW, Fang L, Shatseva T, et al. Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci. 2013;126(Pt 6):1517–30.

    Article  CAS  PubMed  Google Scholar 

  35. Yang X, Du WW, Li H, et al. Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res. 2013;41(21):9688–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fang L, Deng Z, Shatseva T, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8. Oncogene. 2011;30(7):806–21.

    Article  CAS  PubMed  Google Scholar 

  37. Fang L, Du WW, Yang W, et al. MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell Cycle. 2012;11(23):4352–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hazarika S, Farber CR, Dokun AO, et al. MicroRNA-93 controls perfusion recovery after hindlimb ischemia by modulating expression of multiple genes in the cell cycle pathway. Circulation. 2013;127(17):1818–28.

    Article  CAS  PubMed  Google Scholar 

  39. Savita U, Karunagaran D. MicroRNA-106b-25 cluster targets β-TRCP2, increases the expression of Snail and enhances cell migration and invasion in H1299 (non small cell lung cancer) cells. Biochem Biophys Res Commun. 2013;434(4):841–7.

    Article  CAS  PubMed  Google Scholar 

  40. Cascio S, D’Andrea A, Ferla R, et al. MiR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol. 2010;224(1):242–9.

    CAS  PubMed  Google Scholar 

  41. Lee DY, Deng Z, Wang CH, et al. MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci U S A. 2007;104(51):20350–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Deng Z, Yang X, Fang L, et al. Misprocessing and functional arrest of microRNAs by miR-Pirate: roles of miR-378 and miR-17. Biochem J. 2013;450(2):375–86.

    Article  CAS  PubMed  Google Scholar 

  43. Deng Z, Du WW, Fang L, et al. The intermediate filament vimentin mediates microRNA miR-378 function in cellular self-renewal by regulating the expression of the Sox2 transcription factor. J Biol Chem. 2013;288:319–31.

    Article  CAS  PubMed  Google Scholar 

  44. Liu F, Lv Q, Du WW, et al. Specificity of miR-378a-5p targeting rodent fibronectin. Biochim Biophys Acta. 2013;1833(12):3272–85.

    Article  CAS  PubMed  Google Scholar 

  45. Luo L, Ye G, Nadeem L, et al. MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal. J Cell Sci. 2012;125(Pt 13):3124–32.

    Article  CAS  PubMed  Google Scholar 

  46. Pola R, Ling LE, Silver M, et al. The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors. Nat Med. 2001;7(6):706–11.

    Article  CAS  PubMed  Google Scholar 

  47. Hua Z, Lv Q, Ye W, et al. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS ONE. 2006;1, e116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Siragam V, Rutnam ZJ, Yang W, et al. MicroRNA miR-98 inhibits tumor angiogenesis and invasion by targeting activin receptor-like kinase-4 and matrix metalloproteinase-11. Oncotarget. 2012;3(11):1370–85.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Li F, Li XJ, Qiao L, et al. MiR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6. Exp Mol Med. 2014;46:e116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang S, Aurora AB, Johnson BA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Soncin F, Mattot V, Lionneton F, et al. VE-statin, an endothelial repressor of smooth muscle cell migration. EMBO J. 2003;22(21):5700–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fish JE, Santoro MM, Morton SU, et al. MiR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kuhnert F, Mancuso MR, Hampton J, et al. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development. 2008;135(24):3989–93.

    Article  CAS  PubMed  Google Scholar 

  54. Van Solingen C, Seghers L, Bijkerk R, et al. Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J Cell Mol Med. 2009;13(8A):1577–85.

    Article  PubMed  CAS  Google Scholar 

  55. Sasahira T, Kurihara M, Bhawal UK, et al. Downregulation of miR-126 induces angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer. Br J Cancer. 2012;107(4):700–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chen H, Li L, Wang S, et al. Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A. Oncotarget. 2014;5(23):11873–85.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Li Y, Song YH, Li F, et al. MicroRNA-221 regulates high glucose-induced endothelial dysfunction. Biochem Biophys Res Commun. 2009;381(1):81–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Minami Y, Satoh M, Maesawa C, et al. Effect of atorvastatin on microRNA 221 / 222 expression in endothelial progenitor cells obtained from patients with coronary artery disease. Eur J Clin Investig. 2009;39(5):359–67.

    Article  CAS  Google Scholar 

  59. Guo CJ, Pan Q, Li DG, et al. MiR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: an essential role for apoptosis. J Hepatol. 2009;50(4):766–78.

    Article  CAS  PubMed  Google Scholar 

  60. Chen Y, Gorski DH. Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood. 2008;111(3):1217–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. He J, Wu J, Xu NH. MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes. Nucleic Acids Res. 2013;41(1):498–508.

    Article  CAS  PubMed  Google Scholar 

  62. Kuijper S, Turner CJ, Adams RH. Regulation of angiogenesis by Eph–ephrin interactions. Trends Cardiovasc Med. 2007;17(5):145–51.

    Article  CAS  PubMed  Google Scholar 

  63. Ivan M, Harris AL, Martelli F, et al. Hypoxia response and microRNAs: no longer two separate worlds. J Cell Mol Med. 2008;12(5A):1426–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fasanaro P, D’alessandra Y, Stefanoet VD, et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand ephrin-A3. J Biol Chem. 2008;283(23):15878–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fasanaro P, Greco S, Lorenzi M, et al. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem. 2009;284(50):35134–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hu S, Huang M, Li Z, et al. MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation. 2010;122(11 Suppl):S124–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nakamura Y, Patrushev N, Inomata N, et al. Role of protein tyrosine phosphatase 1B in vascular endothelial growth factor signaling and cell-cell adhesions in endothelial cells. Circ Res. 2008;102(10):1182–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Yang X, Rutnam ZJ, Jiao CW, et al. An anti-let-7 sponge decoys and decays endogenous let-7 functions. Cell Cycle. 2012;11(16):3097–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bae ON, Wang JM, Baek SH, et al. Oxidative stress-mediated thrombospondin-2 upregulation impairs bone marrow-derived angiogenic cell function in diabetes mellitus. Arterioscler Thromb Vasc Biol. 2013;33(8):1920–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chen Z, Lai TC, Jan YH, et al. Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis. J Clin Invest. 2013;123(3):1057–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Anand S, Cheresh DA. MicroRNA-mediated regulation of the angiogenic switch. Curr Opin Hematol. 2011;18(3):171–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang S, Olson EN. AngiomiRs-key regulators of angiogenesis. Curr Opin Genet Dev. 2009;19(3):205–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Würdinger T, Tannous BA, Saydam O. MiR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008;14(5):382–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Ma L, Young J, Prabhala H, et al. MiR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12(3):247–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Parmacek MS. MicroRNA-modulated targeting of vascular smooth muscle cells. J Clin Invest. 2009;119(9):2526–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Anand S, Majeti BK, Acevedo LM. MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med. 2010;16(8):909–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yang Z, Wu L, Zhu X, et al. MiR-29a modulates the angiogenic properties of human endothelial cells. Biochem Biophys Res Commun. 2013;434(1):143–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wang J, Wang Y, Wang Y. Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium. J Biol Chem. 2013;288(15):10418–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Rutnam ZJ, Wight TN, Yang BB. miRNAs regulate expression and function of extracellular matrix molecules. Matrix Biol. 2013;32(2):74–85.

    Article  CAS  PubMed  Google Scholar 

  80. Wang W, Zhang E, Lin C. MicroRNAs in tumor angiogenesis. Life Sci. 2015;136:28–35.

    Article  CAS  PubMed  Google Scholar 

  81. Xu Q, Liu LZ, Qian X, et al. MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis. Nucleic Acids Res. 2012;40(2):761–74.

    Article  CAS  PubMed  Google Scholar 

  82. Watanabe HS. Horizons in cancer research. Sunrise: Nova Science Publisher; 2014.

    Google Scholar 

  83. Zhang Y, Wang XY, Xu BH, et al. Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer. Oncol Rep. 2013;30(4):1976–84.

    CAS  PubMed  Google Scholar 

  84. Mathew LK, Skuli N, Mucaj V, et al. MiR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma. Proc Natl Acad Sci U S A. 2014;111(1):291–6.

    Article  CAS  PubMed  Google Scholar 

  85. Seok JK, Skuli N, Mucaj V, et al. MicroRNA-382 induced by HIF-1α is an angiogenic miR targeting the tumor suppressor phosphatase and tensin homolog. Nucleic Acids Res. 2014;42(12):8062–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zheng Y, Li S, Ding Y, et al. The role of miR-18a in gastric cancer angiogenesis. Hepato-Gastroenterology. 2013;60(127):1809–13.

    CAS  PubMed  Google Scholar 

  87. Liu LZ, Li C, Chen Q, et al. MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS ONE. 2011;6(4), e19139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Thum T, Fiedler J. LINCing MALAT1 and angiogenesis. Circ Res. 2014;114(9):1366–8.

    Article  CAS  PubMed  Google Scholar 

  89. Michalik KM, You X, Manavski Y, et al. Long non-coding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res. 2014;114(9):1389–97.

    Article  CAS  PubMed  Google Scholar 

  90. Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014;1839(11):1097–109.

    Article  CAS  PubMed  Google Scholar 

  91. Yuan SX, Yang F, Yang Y, et al. Long non-coding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology. 2012;56(6):2231–41.

    Article  CAS  PubMed  Google Scholar 

  92. Yarmishyn AA, Batagov AO, Tan JZ, et al. HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of non-coding transcriptome. BMC Genomics. 2014;15 Suppl 9:S7.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Huang JL, Zheng L, Hu YW, et al. Characteristics of long non-coding RNA and its relation to hepatocellular carcinoma. Carcinogenesis. 2014;35(3):507–14.

    Article  CAS  PubMed  Google Scholar 

  94. Kunej T, Obsteter J, Pogacar Z, et al. The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring. Crit Rev Clin Lab Sci. 2014;51(6):344–57.

    Article  CAS  PubMed  Google Scholar 

  95. Jiao F, Hu H, Ha T, et al. Long non-coding RNA MALAT-1 enhances stem cell-like phenotypes in pancreatic cancer cells. Int J Mol Sci. 2015;16(4):6677–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zhou Y, Zhang X, Klibanski A. MEG3 non-coding RNA: a tumor suppressor. J Mol Endocrinol. 2012;48(3):R45–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gordon FE, Nutt CL, Cheunsuchon P, et al. Increased expression of angiogenic genes in the brains of mouse Meg3Null embryos. Endocrinology. 2010;151(6):2443–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Im JH, Muschel RJ. New evidence of lncRNA role in tumor progression and metastasis. Hepatobiliary Surg Nutr. 2012;1(1):55–6.

    PubMed  PubMed Central  Google Scholar 

  99. Iaconetti C, Gareri C, Polimeni A, et al. Non-coding RNAs: the “Dark Matter” of cardiovascular pathophysiology. Int J Mol Sci. 2013;4(10):19987–20018.

    Article  CAS  Google Scholar 

  100. Derrien T, Guigó R, Johnson R, et al. The long non-coding RNAs: a new (P)layer in the “Dark Matter”. Front Genet. 2012;2:107. doi:10.3389/fgene.2011.00107. eCollection 2011.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Rutnam ZJ, Yang BB. The non-coding 3’ UTR of CD44 induces metastasis by regulating extracellular matrix functions. J Cell Sci. 2012;125(Pt 8):2075–85.

    Article  CAS  PubMed  Google Scholar 

  102. Fang L, Du WW, Yang X, et al. Versican 3’-untranslated region (3’-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. FASEB J. 2013;27(3):907–19.

    Article  CAS  PubMed  Google Scholar 

  103. Lee SC, Fang L, Wanget CH, et al. A non-coding transcript of nephronectin promotes osteoblast differentiation by modulating microRNA functions. FEBS Lett. 2011;585(16):2610–6.

    Article  CAS  PubMed  Google Scholar 

  104. Jeyapalan Z, Deng ZQ, Shatseva T, et al. Expression of CD44 3’-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis. Nucleic Acids Res. 2011;39(8):3026–41.

    Article  CAS  PubMed  Google Scholar 

  105. Kahai S, Lee SC, Lee DY, et al. MicroRNA miR-378 regulates nephronectin expression modulating osteoblast differentiation by targeting GalNT-7. PLoS ONE. 2009;4(10):e7535.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Rutnam ZJ, Du WW, Yang W, et al. The pseudogene TUSC2P promotes TUSC2 function by binding multiple microRNAs. Nat Commun. 2014;5:2914.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Poliseno L, Salmena L, Zhang JW, et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465(7301):1033–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lee DY, Shatseva T, Jeyapalan Z, et al. A 3’-untranslated region (3’UTR) induces organ adhesion by regulating miR-199a* functions. PLoS ONE. 2009;4(2):e4527.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Leucci E, Patella F, Waageet J, et al. MicroRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep. 2013;3:2535. doi:10.1038/srep02535.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Yoon JH, Abdelmohsen K, Srikantan S, et al. LincRNA-p21 suppresses target mRNA translation. Mol Cell. 2012;47(4):648–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Yoon JH, Abdelmohsen K, Kim J, et al. Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun. 2013;4:2939.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Franklin JL, Rankinb CR, Levyet S, et al. Malignant transformation of colonic epithelial cells by a colon-derived long non-coding RNA. Biochem Biophys Res Commun. 2013;440(1):99–104.

    Article  CAS  PubMed  Google Scholar 

  113. Franco-Zorrilla JM, Valli A, Todesco M, et al. Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet. 2007;39(8):1033–7.

    Article  CAS  PubMed  Google Scholar 

  114. Wang Y, Xu Z, Jiang J, et al. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell. 2013;25(1):69–80.

    Article  CAS  PubMed  Google Scholar 

  115. Yoon JH, Abdelmohsen K, Gorospe M. Functional interactions among microRNAs and long non-coding RNAs. Semin Cell Dev Biol. 2014;34:9–14.

    Article  CAS  PubMed  Google Scholar 

  116. Thum T, Condorelli G. Long non-coding RNAs and microRNAs in cardiovascular pathophysiology. Circ Res. 2015;116(4):751–62.

    Article  CAS  PubMed  Google Scholar 

  117. Paraskevopoulou MD, Georgakilas G, Kostoulas N, et al. DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs. Nucleic Acids Res. 2013;41(Database issue):D239–45.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC; 227937–2012) to BBY, who is the recipient of a Career Investigator Award (CI 7418) from the Heart and Stroke Foundation of Ontario.

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Authors and Affiliations

  1. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, M4N 3M5, Toronto, Canada

    Azam Khorshidi, Preet Dhaliwal & Burton B. Yang

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

    Azam Khorshidi, Preet Dhaliwal & Burton B. Yang

Authors
  1. Azam Khorshidi
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  2. Preet Dhaliwal
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  3. Burton B. Yang
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Correspondence to Burton B. Yang .

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  1. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

    Erwei Song

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© 2016 Springer Science+Business Media Singapore

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Khorshidi, A., Dhaliwal, P., Yang, B.B. (2016). Noncoding RNAs in Tumor Angiogenesis. In: Song, E. (eds) The Long and Short Non-coding RNAs in Cancer Biology. Advances in Experimental Medicine and Biology, vol 927. Springer, Singapore. https://doi.org/10.1007/978-981-10-1498-7_8

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