Emerging Roles of Non-Coding RNAs in the Hypoxic Response

Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Hypoxia is a key component of the tumor microenvironment and represents a well-documented source of therapeutic failure in clinical oncology. Recent work has provided support to the idea that noncoding RNAs (ncRNAs), and in particular microRNAs (miRNAs), may play important roles in the adaptive response to low oxygen in tumors. Specifically, all published studies agree that the induction of microRNA-210 (miR-210) is a consistent feature of the hypoxic response in both normal and transformed cells. miR-210 is a robust target of hypoxia-inducible factor (HIF), and its overexpression has been detected in a variety of diseases with a hypoxic component, including most solid tumors. High levels of miR-210 have been linked to an in vivo hypoxic signature and to adverse prognosis in breast and pancreatic cancer patients. A wide variety of miR-210 targets have been identified, pointing to roles in mitochondrial metabolism, angiogenesis, differentiation, DNA damage response, and cell survival. Such targets are suspected to affect the development of tumors in multiple ways; therefore, an increased knowledge about miR-210’s actions may lead to novel diagnostic and therapeutic approaches in the cancer field.

Keywords

Hypoxia MicroRNA Cancer Biomarker MiR-210 Mitochondria Apoptosis Metabolism 

Notes

Acknowledgments

This work was supported by NIH R01 funding and the American Cancer Society (MI, USA), the Italian Ministry of Health (Ministero della Salute), and the Italian Association for Cancer Research (AIRC).

References

  1. Alaiti MA, Ishikawa M, Masuda H, Simon DI, Jain MK, Asahara T, Costa MA (2012) Up-regulation of miR-210 by vascular endothelial growth factor in ex vivo expanded CD34 +cells enhances cell-mediated angiogenesis. J Cell Mol Med 16:2413–2421PubMedGoogle Scholar
  2. Allegra A, Alonci A, Campo S, Penna G, Petrungaro A, Gerace D, Musolino C (2012) Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer (Review). Int J Oncol 41:1897–1912Google Scholar
  3. Amaral PP, Dinger ME, Mercer TR, Mattick JS (2008) The eukaryotic genome as an RNA machine. Science 319:1787–1789Google Scholar
  4. Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landazuri MO, Enriquez JA (2012) NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab 16:378–386Google Scholar
  5. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233Google Scholar
  6. Benson FE, Baumann P, West SC (1998) Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature 391:401–404Google Scholar
  7. Bindra RS, Schaffer PJ, Meng A, Woo J, Maseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, Glazer PM (2004) Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol 24:8504–8518Google Scholar
  8. Bindra RS, Gibson SL, Meng A, Westermark U, Jasin M, Pierce AJ, Bristow RG, Classon MK, Glazer PM (2005) Hypoxia-induced down-regulation of BRCA1 expression by E2Fs. Cancer Res 65:11597–11604Google Scholar
  9. Biswas S, Roy S, Banerjee J, Hussain SR, Khanna S, Meenakshisundaram G, Kuppusamy P, Friedman A, Sen CK (2010) Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds. Proc Natl Acad Sci U S A 107:6976–6981Google Scholar
  10. Bostjancic E, Zidar N, Glavac D (2009) MicroRNA microarray expression profiling in human myocardial infarction. Dis Markers 27:255–268Google Scholar
  11. Brown JM, Giaccia AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58:1408–1416Google Scholar
  12. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nature reviews. Cancer 6:857–866Google Scholar
  13. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J (2008) hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14:1340–1348Google Scholar
  14. Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, Loscalzo J (2009) MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab 10:273–284Google Scholar
  15. Chapman JR, Taylor MR, Boulton SJ (2012) Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47:497–510Google Scholar
  16. Chen Z, Li Y, Zhang H, Huang P, Luthra R (2010) Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29:4362–4368Google Scholar
  17. Chen WY, Liu WJ, Zhao YP, Zhou L, Zhang TP, Chen G, Shu H (2012) Induction, modulation and potential targets of miR-210 in pancreatic cancer cells. Hepatobiliary Pancreat Dis Int 11:319–324Google Scholar
  18. Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334:1351–1358Google Scholar
  19. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA (2011) MicroRNAs in body fluids–the mix of hormones and biomarkers. Nat Rev Clin Oncol 8:467–477Google Scholar
  20. Crosby ME, Devlin CM, Glazer PM, Calin GA, Ivan M (2009a) Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des 15:3861–3866Google Scholar
  21. Crosby ME, Kulshreshtha R, Ivan M, Glazer PM (2009b) MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res 69:1221–1229Google Scholar
  22. Detmar M (2000) Tumor angiogenesis. J Investig Dermatol Symp Proc 5:20–23Google Scholar
  23. Djuranovic S, Nahvi A, Green R (2011) A parsimonious model for gene regulation by miRNAs. Science 331:550–553Google Scholar
  24. Djuranovic S, Nahvi A, Green R (2012) miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science 336:237–240Google Scholar
  25. Donker RB, Mouillet JF, Nelson DM, Sadovsky Y (2007) The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts. Mol Hum Reprod 13:273–279Google Scholar
  26. Enquobahrie DA, Abetew DF, Sorensen TK, Willoughby D, Chidambaram K, Williams MA (2011) Placental microRNA expression in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 204:e112–121Google Scholar
  27. Fabbri E, Brognara E, Borgatti M, Lampronti I, Finotti A, Bianchi N, Sforza S, Tedeschi T, Manicardi A, Marchelli R, Corradini R, Gambari R (2011a) miRNA therapeutics: delivery and biological activity of peptide nucleic acids targeting miRNAs. Epigenomics 3:733–745Google Scholar
  28. Fabbri E, Manicardi A, Tedeschi T, Sforza S, Bianchi N, Brognara E, Finotti A, Breveglieri G, Borgatti M, Corradini R, Marchelli R, Gambari R (2011b) Modulation of the biological activity of microRNA-210 with peptide nucleic acids (PNAs). ChemMedChem 6:2192–2202Google Scholar
  29. Faraonio R, Salerno P, Passaro F, Sedia C, Iaccio A, Bellelli R, Nappi TC, Comegna M, Romano S, Salvatore G, Santoro M, Cimino F (2012) A set of miRNAs participates in the cellular senescence program in human diploid fibroblasts. Cell Death Differ 19:713–721Google Scholar
  30. Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283:15878–15883Google Scholar
  31. Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, Martelli F (2009) An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem 284:35134–35143Google Scholar
  32. Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, Vojnovic B, Pires das Neves R, Glazer P, Iborra F, Ivan M, Ragoussis J, Harris AL (2010) MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS One 5:e10345PubMedGoogle Scholar
  33. Fasanaro P, Romani S, Voellenkle C, Maimone B, Capogrossi MC, Martelli F (2012) ROD1 Is a Seedless Target Gene of Hypoxia-Induced miR-210. PLoS One 7:e44651PubMedGoogle Scholar
  34. Firth JD, Ebert BL, Pugh CW, Ratcliffe PJ (1994) Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3′ enhancer. Proc Natl Acad Sci U S A 91:6496–6500Google Scholar
  35. Firth JD, Ebert BL, Ratcliffe PJ (1995) Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem 270:1021–21027Google Scholar
  36. Foekens JA, Sieuwerts AM, Smid M, Look MP, Weerd V de, Boersma AW, Klijn JG, Wiemer EA, Martens JW (2008) Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A 105:13021–13026Google Scholar
  37. Gambari R, Fabbri E, Borgatti M, Lampronti I, Finotti A, Brognara E, Bianchi N, Manicardi A, Marchelli R, Corradini R (2011) Targeting microRNAs involved in human diseases: a novel approach for modification of gene expression and drug development. Biochem Pharmacol 82:1416–1429Google Scholar
  38. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899Google Scholar
  39. Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, Homer J, Corbridge R, Cox G, West CM, Ragoussis J, Harris AL (2010) hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer 116:2148–2158Google Scholar
  40. Giannakakis A, Sandaltzopoulos R, Greshock J, Liang S, Huang J, Hasegawa K, Li C, O’Brien-Jenkins A, Katsaros D, Weber BL, Simon C, Coukos G, Zhang L (2008) miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther 7:255–264Google Scholar
  41. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A (2008) Serum microRNAs are promising novel biomarkers. PLoS One 3:e3148PubMedGoogle Scholar
  42. Greco S, Fasanaro P, Castelvecchio S, D’Alessandra Y, Arcelli D, Di Donato M, Malavazos A, Capogrossi MC, Menicanti L, Martelli F (2012) MicroRNA dysregulation in diabetic ischemic heart failure patients. Diabetes 61:1633–1641Google Scholar
  43. Greither T, Grochola LF, Udelnow A, Lautenschlager C, Wurl P, Taubert H (2010) Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 126:73–80Google Scholar
  44. Hammer S, To KK, Yoo YG, Koshiji M, Huang LE (2007) Hypoxic suppression of the cell cycle gene CDC25A in tumor cells. Cell Cycle 6:1919–1926Google Scholar
  45. He J, Wu J, Xu N, Xie W, Li M, Li J, Jiang Y, Yang BB, Zhang Y (2012) MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes. Nucleic Acids Res 41:498–508Google Scholar
  46. Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le QT, Koong AC (2010) Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Transl Oncol 3:109–113Google Scholar
  47. Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, Sun N, Wang X, Martelli F, Robbins RC, Wu JC (2010) MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation 122:124–131Google Scholar
  48. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ (2009) Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell 35:856–867Google Scholar
  49. Iguchi H, Kosaka N, Ochiya T (2010) Versatile applications of microRNA in anti-cancer drug discovery: from therapeutics to biomarkers. Curr Drug Discov Technol 7:95–105Google Scholar
  50. Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4:143–159Google Scholar
  51. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070Google Scholar
  52. Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966Google Scholar
  53. Juan D, Alexe G, Antes T, Liu H, Madabhushi A, Delisi C, Ganesan S, Bhanot G, Liou LS (2010) Identification of a microRNA panel for clear-cell kidney cancer. Urology 75:835–841Google Scholar
  54. Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC Jr, Park ST, Pusztai L, Calin GA (2012) Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 118:2603–2614Google Scholar
  55. Kelly TJ, Souza AL, Clish CB, Puigserver P (2011) A hypoxia-induced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol Cell Biol 31:2696–2706Google Scholar
  56. Kim HW, Haider HK, Jiang S, Ashraf M (2009) Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem 284:3161–33168Google Scholar
  57. Kim HW, Mallick F, Durrani S, Ashraf M, Jiang S, Haider KH (2012) Concomitant activation of miR-107/PDCD10 and Hypoxamir-210/Casp8ap2 and their role in cytoprotection during ischemic preconditioning of stem cells. Antioxid Redox Signal 17:1053–1065Google Scholar
  58. King HW, Michael MZ, Gleadle JM (2012) Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12:421PubMedGoogle Scholar
  59. Kloosterman WP, Plasterk RH (2006) The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450Google Scholar
  60. Krick S, Hanze J, Eul B, Savai R, Seay U, Grimminger F, Lohmeyer J, Klepetko W, Seeger W, Rose F (2005) Hypoxia-driven proliferation of human pulmonary artery fibroblasts: cross-talk between HIF-1alpha and an autocrine angiotensin system. FASEB J 19:857–859Google Scholar
  61. Kulshreshtha R, Ferracin M, Negrini M, Calin GA, Davuluri RV, Ivan M (2007) Regulation of microRNA expression: the hypoxic component. Cell Cycle 6:1426–1431Google Scholar
  62. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, Calin GA, Ivan M (2007) A microRNA signature of hypoxia. Mol Cell Biol 27:1859–1867Google Scholar
  63. Landau DA, Slack FJ (2011) MicroRNAs in mutagenesis, genomic instability, and DNA repair. Semin Oncol 38:743–751Google Scholar
  64. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327:198–201Google Scholar
  65. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141:672–675Google Scholar
  66. Lee DW, Futami M, Carroll M, Feng Y, Wang Z, Fernandez M, Whichard Z, Chen Y, Kornblau S, Shpall EJ, Bueso-Ramos CE, Corey SJ (2012) Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155. Oncogene 31:4085–4094Google Scholar
  67. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854Google Scholar
  68. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060Google Scholar
  69. Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N, Helin K (1993) The retinoblastoma protein binds to a family of E2F transcription factors. Mol Cell Biol 13:7813–7825Google Scholar
  70. Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS, Nevins JR (1998) E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev 12:2120–2130Google Scholar
  71. Leung AK, Sharp PA (2010) MicroRNA functions in stress responses. Mol Cell 40:205–215Google Scholar
  72. Levy AP, Levy NS, Wegner S, Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270:13333–13340Google Scholar
  73. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20Google Scholar
  74. Li T, Cao H, Zhuang J, Wan J, Guan M, Yu B, Li X, Zhang W (2011) Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans. Clin Chim Acta 412:66–70Google Scholar
  75. Liu F, Lou YL, Wu J, Ruan QF, Xie A, Guo F, Cui SP, Deng ZF, Wang Y (2012) Upregulation of MicroRNA-210 regulates renal angiogenesis mediated by activation of VEGF signaling pathway under ischemia/perfusion injury in vivo and in vitro. Kidney Blood Press Res 35:182–191Google Scholar
  76. Liu M, Liu H, Dudley SC Jr (2010) Reactive oxygen species originating from mitochondria regulate the cardiac sodium channel. Circ Res 107:967–974Google Scholar
  77. Lou YL, Guo F, Liu F, Gao FL, Zhang PQ, Niu X, Guo SC, Yin JH, Wang Y, Deng ZF (2012) miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochem 370:45–51Google Scholar
  78. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838Google Scholar
  79. Merlo A, Quiros SB de, Secades P, Zambrano I, Balbin M, Astudillo A, Scola B, Aristegui M, Suarez C, Chiara MD (2012) Identification of a Signaling Axis HIF-1alpha/MicroRNA-210/ISCU independent of sdh mutation that defines a subgroup of head and neck paragangliomas. J Clin Endocrinol Metab 97:E2194–2200PubMedGoogle Scholar
  80. Michael MZ SMOC, Holst Pellekaan NG van, Young GP, James RJ (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1:882–891Google Scholar
  81. Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y (2009) miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS lett 583:2263–2268Google Scholar
  82. Mochel F, Knight MA, Tong WH, Hernandez D, Ayyad K, Taivassalo T, Andersen PM, Singleton A, Rouault TA, Fischbeck KH, Haller RG (2008) Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet 82:652–660Google Scholar
  83. Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K (2006) Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25:2537–2545Google Scholar
  84. Nakamura H, Tanimoto K, Hiyama K, Yunokawa M, Kawamoto T, Kato Y, Yoshiga K, Poellinger L, Hiyama E, Nishiyama M (2008) Human mismatch repair gene, MLH1, is transcriptionally repressed by the hypoxia-inducible transcription factors, DEC1 and DEC2. Oncogene 27:4200–4209Google Scholar
  85. Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2:423–427Google Scholar
  86. Pasini B, Stratakis CA (2009) SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes. J Intern Med 266:19–42Google Scholar
  87. Pineles BL, Romero R, Montenegro D, Tarca AL, Han YM, Kim YM, Draghici S, Espinoza J, Kusanovic JP, Mittal P, Hassan SS, Kim CJ (2007) Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol 196:e261–266Google Scholar
  88. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T (2007) MicroRNA expression profiling in prostate cancer. Cancer Res 67:6130–6135Google Scholar
  89. Puissegur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V, Fourre S, Magnone V, Ricci JE, Pouyssegur J, Gounon P, Hofman P, Barbry P, Mari B (2011) miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ 18:465–478Google Scholar
  90. Pulkkinen K, Malm T, Turunen M, Koistinaho J, Yla-Herttuala S (2008) Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210. FEBS Lett 582:2397–2401Google Scholar
  91. Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, He Z, Mo D (2010) A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genomics 11:320PubMedGoogle Scholar
  92. Semenza GL (2010) Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29:625–634Google Scholar
  93. Semenza GL (2010) Vascular responses to hypoxia and ischemia. Arterioscler Thromb Vasc Biol 30:648–652Google Scholar
  94. Semenza GL, Roth PH, Fang HM, Wang GL (1994) Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 269:23757–23763Google Scholar
  95. Shinohara A, Ogawa T (1998) Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature 391:404–407Google Scholar
  96. Simone NL, Soule BP, Ly D, Saleh AD, Savage JE, Degraff W, Cook J, Harris CC, Gius D, Mitchell JB (2009) Ionizing radiation-induced oxidative stress alters miRNA expression. PLoS One 4:e6377PubMedGoogle Scholar
  97. Sitohy B, Nagy JA, Dvorak HF (2012) Anti-VEGF/VEGFR therapy for cancer: reassessing the target. Cancer Res 72:1909–1914Google Scholar
  98. Stenvang J, Silahtaroglu AN, Lindow M, Elmen J, Kauppinen S (2008) The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Semin Cancer Biol 18:89–102Google Scholar
  99. Sung P, Robberson DL (1995) DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell 82:453–461Google Scholar
  100. Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, Laake LW van, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J (2007) MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 116:258–267Google Scholar
  101. Tong WH, Rouault TA (2006) Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab 3:199–210Google Scholar
  102. Toyama T, Kondo N, Endo Y, Sugiura H, Yoshimoto N, Iwasa M, Takahashi S, Fujii Y, Yamashita H (2012) High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients. Jpn J Clin Oncol 42:256–263Google Scholar
  103. Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G (2011) MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem 286:420–428Google Scholar
  104. Rooij E van, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci the U S A 103:18255–18260Google Scholar
  105. Wan G, Mathur R, Hu X, Zhang X, Lu X (2011) miRNA response to DNA damage. Trends Biochem Sci 36:478–484Google Scholar
  106. Wang GL, Semenza GL (1993) General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A 90:4304–4308Google Scholar
  107. Wang GL, Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270:1230–1237Google Scholar
  108. Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92:5510–5514Google Scholar
  109. Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, Sen S (2009) MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila) 2:807–813Google Scholar
  110. Wang S, Olson EN (2009) AngiomiRs–key regulators of angiogenesis. Curr Opin Genet Dev 19:205–211Google Scholar
  111. Wilson WR, Hay MP (2011) Targeting hypoxia in cancer therapy. Nat Rev Cancer 11:393–410Google Scholar
  112. Wu F, Yang Z, Li G (2009) Role of specific microRNAs for endothelial function and angiogenesis. Biochem Biophys Res Commun 386:549–553Google Scholar
  113. Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH (2009) Repression of the miR-929217–92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J 28:2719–2732Google Scholar
  114. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198Google Scholar
  115. Yang W, Sun T, Cao J, Liu F, Tian Y, Zhu W (2012) Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp Cell Res 318:944–954Google Scholar
  116. Ying Q, Liang L, Guo W, Zha R, Tian Q, Huang S, Yao J, Ding J, Bao M, Ge C, Yao M, Li J, He X (2011) Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology 54:2064–2075Google Scholar
  117. Yoshioka Y, Kosaka N, Ochiya T, Kato T (2012) Micromanaging Iron Homeostasis: Hypoxia-Inducible Micro-RNA-210 suppresses iron homeostasis-related proteins. J Biol Chem 287:34110–34119Google Scholar
  118. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL (2007) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11:407–420Google Scholar
  119. Zhang X, Wan G, Berger FG, He X, Lu X (2011) The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell 41:371–383Google Scholar
  120. Zhang Z, Sun H, Dai H, Walsh RM, Imakura M, Schelter J, Burchard J, Dai X, Chang AN, Diaz RL, Marszalek JR, Bartz SR, Carleton M, Cleary MA, Linsley PS, Grandori C (2009) MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle 8:2756–2768Google Scholar
  121. Zhao A, Li G, Peoc’h M, Genin C, Gigante M (2012) Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol 94:115–120Google Scholar
  122. Zhu XM, Han T, Sargent IL, Yin GW, Yao YQ (2009) Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol 200:e661–667Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of MedicineIndiana UniversityIndianapolisUSA
  2. 2.Department of Microbiology and ImmunologyIndiana UniversityIndianapolisUSA
  3. 3.Molecular Cardiology LaboratoryIRCCS-Policlinico San DonatoMilanItaly

Personalised recommendations