HypoxamiRs and cancer: From biology to targeted therapy

Antioxidants and Redox Signaling

Volumn 21, Issue 8, 2014, Pages 1220-1238

  Gee, Harriet E ^a,b   Ivan, Cristina ^c   Calin, George A ^c   Ivan, Mircea ^d  

^a ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^d INDIANA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; GLYCEROL 3 PHOSPHATE DEHYDROGENASE; HYPOXIA INDUCIBLE FACTOR; MICRORNA; MICRORNA 210; OXYGEN; SCAFFOLD PROTEIN; MIRN210 MICRORNA, HUMAN;

APOPTOSIS; CANCER CELL; CANCER PROGNOSIS; CELL CYCLE; CELL VIABILITY; DNA DAMAGE; FEEDBACK SYSTEM; GENE INTERACTION; GENE OVEREXPRESSION; GENETIC REGULATION; HUMAN; HYPOXIA; MITOCHONDRIAL RESPIRATION; MOLECULARLY TARGETED THERAPY; NEOPLASM; NONHUMAN; OXYGEN TENSION; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PLEIOTROPY; PRIORITY JOURNAL; REVIEW; TUMOR MICROENVIRONMENT; ANIMAL; CELL HYPOXIA; GENE EXPRESSION REGULATION; METABOLISM; MITOCHONDRION; PATHOLOGY; PHYSIOLOGY; VASCULARIZATION;

ANIMALS; APOPTOSIS; CELL HYPOXIA; DNA DAMAGE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICRORNAS; MITOCHONDRIA; MOLECULAR TARGETED THERAPY; NEOPLASMS; TUMOR MICROENVIRONMENT;

EID: 84907369198     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2013.5639     Document Type: Review

References (206)

1. Alaiti MA, Ishikawa M, Masuda H, Simon DI, Jain MK, Asahara T, and Costa MA. 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: 2413-2421, 2012
2. Allegra A, Alonci A, Campo S, Penna G, Petrungaro A, Gerace D, and Musolino C. Circulating microRNAs: New biomarkers in Diagnosis, prognosis and treatment of cancer (Review). Int J Oncol 41: 1897-1912, 2012
3. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, and Bartel DP. The impact of microRNAs on protein output. Nature 455: 64-71, 2008
4. Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 136: 215-233, 2009
5. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, Mey Avd, Taschner PEM, Rubinstein WS, Myers EN, Richard CW, Cornelisse CJ, Devilee P, and Devlin B. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287: 848-851, 2000
6. Beasley NJ, Leek R, Alam M, Turley H, Cox GJ, Gatter K, Millard P, Fuggle S, and Harris AL. Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: Relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res 62: 2493-2497, 2002
7. Benson FE, Baumann P, and West SC. Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature 391: 401-404, 1998
8. Betel D, Wilson M, Gabow A, Marks DS, and Sander C. The microRNA.org resource: Targets and expression. Nucleic Acids Res 36: D149-D153, 2008
9. Bindra R, Crosby M, and Glazer P. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev 26: 249-260, 2007
10. Bindra RS, Schaffer PJ, Meng A, Woo J, Maseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, and Glazer PM. Alterations in DNA repair gene expression under hypoxia: Elucidating the mechanisms of hypoxia-induced genetic instability. Ann N Y Acad Sci 1059: 184-195, 2005
11. Biswas S, Roy S, Banerjee J, Hussain S-RA, Khanna S, Meenakshisundaram G, Kuppusamy P, Friedman A, and Sen CK. 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: 6976-6981, 2010
12. Brown NS and Bicknell R. Hypoxia and oxidative stress in breast cancer. Oxidative stress: Its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 3: 323-327, 2001
13. Brugarolas J. Renal-cell carcinoma-molecular pathways and therapies. N Engl J Med 356: 185-187, 2007
14. Bruning U, Cerone L, Neufeld Z, Fitzpatrick SF, Cheong A, Scholz CC, Simpson DA, Leonard MO, Tambuwala MM, Cummins EP, and Taylor CT. MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol 31: 4087-4096, 2011
15. Buffa FM, Camps C, Winchester L, Snell CE, Gee HE, Sheldon H, Taylor M, Harris AL, and Ragoussis J. micro-RNA-Associated progression pathways and potential therapeutic targets identified by integrated mRNA and micro-RNA expression profiling in breast cancer. Cancer Res 71: 5635-5645, 2011
16. Bunoust O, Devin A, Avéret N, Camougrand N, and Rigoulet M. Competition of electrons to enter the respiratory chain: A new regulatory mechanism of oxidative metabolism in Saccharomyces cerevisiae. J Biol Chem 280: 3407-3413, 2005
17. Bushati N and Cohen SM. microRNA functions. Annu Rev Cell Dev Biol 23: 175-205, 2007
18. Busk M, Horsman MR, Jakobsen S, Bussink J, van Der Kogel A, and Overgaard J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging 35: 2294-2303, 2008
19. Cai H, Lin L, Tang M, Wang Z. Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma. Med Oncol 30: 499, 2013
20. Calin GA and Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 6: 857-866, 2006
21. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, and Ragoussis J. hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14: 1340-1348, 2008
22. Cardenas-Navia LI, Mace D, Richardson RA, Wilson DF, Shan S, and Dewhirst MW. The pervasive presence of fluctuating oxygenation in tumors. Cancer Res 68: 5812-5819, 2008
23. Cascio S, D'Andrea A, Ferla R, Surmacz E, Gulotta E, Amodeo V, Bazan V, Gebbia N, and Russo A. miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol 224: 242-249, 2010
24. Cha ST, Chen PS, Johansson G, Chu CY, Wang MY, Jeng YM, Yu SL, Chen JS, Chang KJ, Jee SH, Tan CT, Lin MT, and Kuo ML. MicroRNA-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis. Cancer Res 70: 2675-2685, 2010
25. Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, and Loscalzo J. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab 10: 273-284, 2009
26. Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, and Schumacker PT. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: A mechanism of O2 sensing. J Biol Chem 275: 25130-25138, 2000
27. Chen H-Y, Lin Y-M, Chung H-C, Lang Y-D, Lin C-J, Huang J, Wang W-C, Lin F-M, Chen Z, Huang H-D, Shyy JY-J, Liang J-T, and Chen R-H. miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer Res 72: 3631-3641, 2012
28. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, and Zhang CY. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18: 997-1006, 2008
29. Chen Z, Lai TC, Jan YH, Lin FM, Wang WC, Xiao H, Wang YT, Sun W, Cui X, Li YS, Fang T, Zhao H, Padmanabhan C, Sun R, Wang DL, Jin H, Chau GY, Huang HD, Hsiao M, and Shyy JY. Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis. J Clin Invest 123: 1057-1067, 2013
30. Chen Z, Li Y, Zhang H, Huang P, and Luthra R. Hypoxiaregulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29: 4362-4368, 2010
31. Cheng AM, Byrom MW, Shelton J, and Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33: 1290-1297, 2005
32. Chio C-C, Lin J-W, Cheng H-A, Chiu W-T, Wang Y-H, Wang J-J, Hsing C-H, and Chen R-M. MicroRNA-210 targets antiapoptotic Bcl-2 expression and mediates hypoxiainduced apoptosis of neuroblastoma cells. Arch Toxicol [Epub ahead of print]; DOI: 10.1007/s00204-012-0965-5, 2012
33. Cho WC, Chow AS, Au JS. Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation. Eur J Cancer 45: 2197-206, 2009
34. Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, and Farace MG. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334: 1351-1358, 2005
35. Cicchillitti L, Di Stefano V, Isaia E, Crimaldi L, Fasanaro P, Ambrosino V, Antonini A, Capogrossi MC, Gaetano C, Piaggio G, and Martelli F. Hypoxia-inducible factor 1-A induces miR-210 in normoxic differentiating myoblasts. J Biol Chem 287: 44761-44771, 2012
36. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, and Calin GA. MicroRNAs in body fluids-The mix of hormones and biomarkers. Nat Rev Clin Oncol 8: 467-477, 2011
37. Crosby ME, Kulshreshtha R, Ivan M, and Glazer PM. MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res 69: 1221-1229, 2009
38. Dejean E, Renalier MH, Foisseau M, Agirre X, Joseph N, de Paiva GR, Al Saati T, Soulier J, Desjobert C, Lamant L, Prosper F, Felsher DW, Cavaille J, Prats H, Delsol G, Giuriato S, and Meggetto F. Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas. Leukemia 25: 1882-1890, 2011
39. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 8: 705-713, 2008
40. Denko NC, Fontana LA, Hudson KM, Sutphin PD, Raychaudhuri S, Altman R, and Giaccia AJ. Investigating hypoxic tumor physiology through gene expression patterns. Oncogene 22: 5907-5914, 2003
41. Devlin C, Greco S, Martelli F, and Ivan M. miR-210: More than a silent player in hypoxia. IUBMB Life 63: 94-100, 2011
42. Djuranovic S, Nahvi A, and Green R. A parsimonious model for gene regulation by miRNAs. Science 331: 550-553, 2011
43. Djuranovic S, Nahvi A, and Green R. miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science 336: 237-240, 2012
44. Donker R, Mouillet J, Nelson D, and Sadovsky Y. The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts. Mol Hum Reprod 13: 273-279, 2007
45. Du R, Sun W, Xia L, Zhao A, Yu Y, Zhao L, Wang H, Huang C, and Sun S. Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells. PLoS One 7: E30771, 2012
46. Fabbri E, Brognara E, Borgatti M, Lampronti I, Finotti A, Bianchi N, Sforza S, Tedeschi T, Manicardi A, Marchelli R, Corradini R, and Gambari R. miRNA therapeutics: Delivery and biological activity of peptide nucleic acids targeting miRNAs. Epigenomics 3: 733-745, 2011
47. Faraonio R, Salerno P, Passaro F, Sedia C, Iaccio A, Bellelli R, Nappi TC, Comegna M, Romano S, Salvatore G, Santoro M, and Cimino F. A set of miRNAs participates in the cellular senescence program in human Diploid fibroblasts. Cell Death Differ 19: 713-721, 2012
48. Fasanaro P, D'Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, and Martelli F. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand ephrin-A3. J Biol Chem 283: 15878-15883, 2008
49. Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, and Martelli F. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem 284: 35134-35143, 2009
50. Fasanaro P, Romani S, Voellenkle C, Maimone B, Capogrossi MC, and Martelli F. ROD1 is a seedless target gene of hypoxia-induced miR-210. PLoS One 7: E44651, 2012
51. 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, and Harris AL. 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: E10345, 2010
52. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AWM, Klijn JGM, Wiemer EAC, and Martens JWM. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A 105: 13021-13026, 2008
53. Fridman E, Dotan Z, Barshack I, David MB, Dov A, Tabak S, Zion O, Benjamin S, Benjamin H, Kuker H, Avivi C, Rosenblatt K, Polak-Charcon S, Ramon J, Rosenfeld N, Spector Y. Accurate molecular classification of renal tumors using microRNA expression. J Mol Diagn 12: 687-96, 2010
54. Gambari R, Fabbri E, Borgatti M, Lampronti I, Finotti A, Brognara E, Bianchi N, Manicardi A, Marchelli R, and Corradini R. Targeting microRNAs involved in human Diseases: A novel approach for modification of gene expression and drug development. Biochem Pharmac 82: 1416-1429, 2011
55. Garzon R, Calin GA, and Croce CM. MicroRNAs in cancer. Annu Rev Med 60: 167-179, 2009
56. Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, Homer J, Corbridge R, Cox G, West CML, Ragoussis J, and Harris AL. hsa-miR-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer 116: 2148-2158, 2010
57. Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y, and Ramakrishnan S. Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-Alpha isoforms and promotes angiogenesis. J Clin Invest 120: 4141-4154, 2010
58. Giannakakis A, Sandaltzopoulos R, Greshock J, Liang S, Huang J, Hasegawa K, Li C, O"Brien-Jenkins A, Katsaros D, Weber B, Simon C, Coukos G, and Zhang L. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther 7: 255-264, 2008
59. 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, and Chajut A. Serum microRNAs are promising novel biomarkers. PLoS One 3: E3148, 2008
60. Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, Latif F, Liu S, Chen F, Duh FM, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 7: 85-90, 1994
61. Gordan JD, Thompson CB, and Simon MC. HIF and c-Myc: Sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 12: 108-113, 2007
62. Gottlieb E and Tomlinson IP. Mitochondrial tumour suppressors: A genetic and biochemical update. Nat Rev Cancer 5: 857-866, 2005
63. Gou D, Ramchandran R, Peng X, Yao L, Kang K, Sarkar J, Wang Z, Zhou G, and Raj JU. miR-210 has an antiapoptotic effect in pulmonary artery smooth muscle cells during hypoxia. Am J Physiol Lung Cell Mol Physiol 303: L682-L691, 2012
64. Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, and Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 126: 73-80, 2010
65. Greither T, Würl P, Grochola L, Bond G, Bache M, Kappler M, Lautenschlä ger C, Holzhausen HJ, Wach S, Eckert AW, and Taubert H. Expression of microRNA 210 associates with poor survival and age of tumor onset of soft-Tissue sarcoma patients. Int J Cancer 130: 1230-1235, 2012
66. Grosso S, Doyen J, Parks SK, Bertero T, Paye A, Cardinaud B, Gounon P, Lacas-Gervais S, Noel A, Pouyssegur J, Barbry P, Mazure NM, and Mari B. MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death Dis 4: E544, 2013
67. Guo H, Ingolia NT, Weissman JS, and Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466: 835-840, 2010
68. Guzy RD and Schumacker PT. Oxygen sensing by mitochondria at complex III: The paradox of increased reactive oxygen species during hypoxia. Exp Physiol 91: 807-819, 2006
69. Hammer S, To KK, Yoo YG, Koshiji M, and Huang LE. Hypoxic suppression of the cell cycle gene CDC25A in tumor cells. Cell Cycle 6: 1919-1926, 2007
70. Hanahan D and Weinberg Robert A. Hallmarks of cancer: The next generation. Cell 144: 646-674, 2011
71. Hazarika S, Farber CR, Dokun AO, Pitsillides AN, Wang T, Lye RJ, and Annex BH. MicroRNA-93 controls perfusion recovery following hind-limb ischemia by modulating expression of multiple genes in the cell cycle pathway. Circulation 127: 1818-1828, 2013
72. He J, Wu J, Xu N, Xie W, Li M, Li J, Jiang Y, Yang BB, and Zhang Y. MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes. Nucleic Acids Res 41: 498-508, 2012
73. He M, Wang QY, Yin QQ, Tang J, Lu Y, Zhou CX, Duan CW, Hong DL, Tanaka T, Chen GQ, and Zhao Q. HIF-1alpha downregulates miR-17/20a directly targeting p21 and STAT3: A role in myeloid leukemic cell differentiation. Cell Death Differ 20: 408-418, 2013
74. Hebert C, Norris K, Scheper MA, Nikitakis N, and Sauk JJ. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer 6: 5, 2007
75. Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le Q-T, and Koong AC. Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Transl Oncol 3: 109-113, 2010
76. Hong L, Yang J, Han Y, Lu Q, Cao J, and Syed L. High expression of miR-210 predicts poor survival in patients with breast cancer: A meta-Analysis. Gene 507: 135-138, 2012
77. Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, Sun N, Wang X, Martelli F, Robbins RC, and Wu JC. MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation 122: S124-S131, 2010
78. Hua Z, Lv Q, Ye W, Wong CK, Cai G, Gu D, Ji Y, Zhao C, Wang J, Yang BB, and Zhang Y. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1: E116, 2006
79. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le Q-T, and Giaccia AJ. Hypoxiainducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell 35: 856-867, 2009
80. Huang X, Le Q-T, and Giaccia AJ. MiR-210- micromanager of the hypoxia pathway. Trends Mol Med 16: 230-237, 2010
81. Hummel R, Hussey DJ, and Haier J. MicroRNAs: Predictors and modifiers of chemo- And radiotherapy in Different tumour types. Eur J Cancer 46: 298-311, 2010
82. Hurlin PJ, Queva C, and Eisenman RN. Mnt, a novel Maxinteracting protein is coexpressed with Myc in proliferating cells and mediates repression at Myc binding sites. Genes Dev 11: 44-58, 1997
83. Iorio MV and Croce CM. MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4: 143-159, 2012
84. 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, and Croce CM. MicroRNA gene expression Deregulation in human breast cancer. Cancer Res 65: 7065-7070, 2005
85. Ivan M, Harris AL, Martelli F, and Kulshreshtha R. Hypoxia response and microRNAs: No longer two separate worlds. J Cell Mol Med 12: 1426-1431, 2008
86. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, and Kaelin WG, Jr. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science 292: 464-468, 2001
87. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, and Ratcliffe PJ. Targeting of HIF-Alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292: 468-472, 2001
88. Janssens GO, Rademakers SE, Terhaard CH, Doornaert PA, Bijl HP, van Den Ende P, Chin A, Marres HA, de Bree R, van Der Kogel AJ, Hoogsteen IJ, Bussink J, Span PN, and Kaanders JH. Accelerated radiotherapy with carbogen and nicotinamide for laryngeal cancer: Results of a phase III randomized trial. J Clin Oncol 30: 1777-1783, 2012
89. Jiang J, Tang YL, and Liang XH. EMT: A new vision of hypoxia promoting cancer progression. Cancer Biol Ther 11: 714-723, 2011
90. Juan D, Alexe G, Antes T, Liu H, Madabhushi A, Delisi C, Ganesan S, Bhanot G, and Liou LS. Identification of a microRNA panel for clear-cell kidney cancer. Urology 75: 835-841, 2010
91. Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC, Jr., Park ST, Pusztai L, and Calin GA. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 118: 2603-2614, 2012
92. Karginov FV, Conaco C, Xuan Z, Schmidt BH, Parker JS, Mandel G, and Hannon GJ. A biochemical approach to identifying microRNA targets. Proc Natl Acad Sci U S A 104: 19291-19296, 2007
93. Kelly TJ, Souza AL, Clish CB, and Puigserver P. A hypoxiainduced positive feedback loop promotes hypoxiainducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol Cell Biol 31: 2696-2706, 2011
94. Kim HW, Haider HK, Jiang S, and Ashraf M. Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-Associated protein 2. J Biol Chem 284: 33161-33168, 2009
95. Kim HW, Mallick F, Durrani S, Ashraf M, Jiang S, and Haider KH. 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: 1053-1065, 2012
96. Kim J-W and Dang CV. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res 66: 8927-8930, 2006
97. Kim JH, Park SG, Song SY, Kim JK, and Sung JH. Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2. Cell Death Dis 4: E588, 2013
98. King HW, Michael MZ, and Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12: 421, 2012
99. Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos C, Turley H, Talks K, Gatter KC, and Harris AL. Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-And-neck cancer. Int J Radiat Oncol Biol Phys 53: 1192-1202, 2002
100. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, and Rajewsky N. Combinatorial microRNA target predictions. Nat Genet 37: 495-500, 2005
101. Krick S, Hanze J, Eul B, Savai R, Seay U, Grimminger F, Lohmeyer J, Klepetko W, Seeger W, and Rose F. Hypoxiadriven proliferation of human pulmonary artery fibroblasts: Cross-Talk between HIF-1alpha and an autocrine angiotensin system. FASEB J 19: 857-859, 2005
102. Kulshreshtha R, Davuluri RV, Calin GA, and Ivan M. A microRNA component of the hypoxic response. Cell Death Differ 15: 667-671, 2008
103. Kulshreshtha R, Ferracin M, Negrini M, Calin GA, Davuluri RV, and Ivan M. Regulation of microRNA expression: The hypoxic component. Cell Cycle 6: 1426-1431, 2007
104. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu C-G, Croce CM, Negrini M, Calin GA, and Ivan M. A microRNA signature of hypoxia. Mol Cell Biol 27: 1859-1867, 2007
105. Kumar K, Wigfield S, Gee HE, Devlin CM, Singleton D, Li JL, Buffa F, Huffman M, Sinn AL, Silver J, Turley H, Leek R, Harris AL, and Ivan M. Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse xenografts. J Mol Med (Berl) 91: 749-758, 2013
106. Landau DA and Slack FJ. MicroRNAs in mutagenesis, genomic instability, and DNA repair. Semin Oncol 38: 743-751, 2011
107. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, and Orum H. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327: 198-201, 2010
108. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260: 1317-1320, 1993
109. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CSR, and Harris AL. Detection of elevated levels of tumour-Associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141: 672-675, 2008
110. Lee Y, Jeon K, Lee J-T, Kim S, and Kim VN. MicroRNA maturation: Stepwise processing and subcellular localization. EMBO J 21: 4663-4670, 2002
111. Lees JA, Saito M, Vidal M, Valentine M, Look T, Harlow E, Dyson N, and Helin K. The retinoblastoma protein binds to a family of E2F transcription factors. Mol Cell Biol 13: 7813-7825, 1993
112. Lei Z, Li B, Yang Z, Fang H, Zhang GM, Feng ZH, and Huang B. Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One 4: E7629, 2009
113. Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS, and Nevins JR. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev 12: 2120-2130, 1998
114. Lewis BP, Burge CB, and Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120: 15-20, 2005
115. Lewis BP, Shih Ih, Jones-Rhoades MW, Bartel DP, and Burge CB. Prediction of mammalian microRNA targets. Cell 115: 787-798, 2003
116. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, and Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433: 769-773, 2005
117. Lin SC, Wang CC, Wu MH, Yang SH, Li YH, and Tsai SJ. Hypoxia-induced microRNA-20a expression increases ERK phosphorylation and angiogenic gene expression in endometriotic stromal cells. J Clin Endocrinol Metab 97: E1515-E1523, 2012
118. Liu M, Liu H, and Dudley SC, Jr. Reactive oxygen species originating from mitochondria regulate the cardiac sodium channel. Circ Res 107: 967-974, 2010
119. Liu Y, Cox SR, Morita T, and Kourembanas S. Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells: Identification of a 5¢ enhancer. Circ Res 77: 638-643, 1995
120. Liu Y, Han Y, Zhang H, Nie L, Jiang Z, Fa P, Gui Y, and Cai Z. Synthetic miRNA-mowers targeting miR-183-96-182 cluster or miR-210 inhibit growth and migration and induce apoptosis in bladder cancer cells. PLoS One 7: E52280, 2012
121. Lou YL, Guo F, Liu F, Gao FL, Zhang PQ, Niu X, Guo SC, Yin JH, Wang Y, and Deng ZF. miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochem 370: 45-51, 2012
122. 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, and Golub TR. Micro-RNA expression profiles classify human cancers. Nature 435: 834-838, 2005
123. Lui W, Pourmand N, Patterson B, and Fire A. Patterns of known and novel small RNAs in human cervical cancer. Cancer Res 67: 6031-6043, 2007
124. Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stühler K, Meyer HE, and Reifenberger G. Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol 20: 539-550, 2009
125. McCormick RI, Blick C, Ragoussis J, Schoedel J, Mole DR, Young AC, Selby PJ, Banks RE, and Harris AL. miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer 108: 1133-1142, 2013
126. Merlo A, de Quiros SB, Secades P, Zambrano I, Balbin M, Astudillo A, Scola B, Aristegui M, Suarez C, Chiara MD. 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: E2194-200, 2012
127. Meroni G, Reymond A, Alcalay M, Borsani G, Tanigami A, Tonlorenzi R, Nigro CL, Messali S, Zollo M, Ledbetter DH, Brent R, Ballabio A, and Carrozzo R. Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor. EMBO J 16: 2892-2906, 1997
128. Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP, and James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1: 882-891, 2003
129. Miko E, Czimmerer Z, Csanky E, Boros G, Buslig J, Dezso B, Scholtz B. Differentially expressed microRNAs in small cell lung cancer. Exp Lung Res 35: 646-64, 2009
130. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, and Tewari M. Circulating micro-RNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105: 10513-10518, 2008
131. Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, and Shimotohno K. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-Tumorous tissues. Oncogene 25: 2537-2545, 2006
132. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 417: 1-13, 2009
133. Mutharasan RK, Nagpal V, Ichikawa Y, and Ardehali H. microRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- And p53-dependent pathways and exerts cytoprotective effects. Am J Physiol Heart Circ Physiol 301: H1519-H1530, 2011
134. Nakada C, Tsukamoto Y, Matsuura K, Nguyen TL, Hijiya N, Uchida T, Sato F, Mimata H, Seto M, and Moriyama M. Overexpression of miR-210, a downstream target of HIF1a, causes centrosome amplification in renal carcinoma cells. J Pathol 224: 280-288, 2011
135. Nakamura Y, Patrushev N, Inomata H, Mehta D, Urao N, Kim HW, Razvi M, Kini V, Mahadev K, Goldstein BJ, McKinney R, Fukai T, and Ushio-Fukai M. Role of protein tyrosine phosphatase 1B in vascular endothelial growth factor signaling and cell-cell adhesions in endothelial cells. Circ Res 102: 1182-1191, 2008
136. Nordsmark M, Bentzen SM, Rudat V, Brizel D, Lartigau E, Stadler P, Becker A, Adam M, Molls M, Dunst J, Terris DJ, and Overgaard J. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol 77: 18-24, 2005
137. Place RF, Li LC, Pookot D, Noonan EJ, and Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 105: 1608-1613, 2008
138. Polytarchou C, Iliopoulos D, Hatziapostolou M, Kottakis F, Maroulakou I, Struhl K, and Tsichlis PN. Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen Deprivation. Cancer Res 71: 4720-4731, 2011
139. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res 67: 6130-5, 2007
140. Presneau N, Eskandarpour M, Shemais T, Henderson S, Halai D, Tirabosco R, Flanagan AM. MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression. Br J Cancer 108: 964-72, 2013
141. Presti JC, Jr., Rao PH, Chen Q, Reuter VE, Li FP, Fair WR, and Jhanwar SC. Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. Cancer Res 51: 1544-1552, 1991
142. 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, and Mari B. 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: 465-478, 2011
143. Qiu S, Lin S, Hu D, Feng Y, Tan Y, Peng Y. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients. J Transl Med 11: 10, 2013
144. Redova M, Poprach A, Besse A, Iliev R, Nekvindova J, Lakomy R, Radova L, Svoboda M, Dolezel J, Vyzula R, and Slaby O. MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal cell carcinoma. Tumour Biol 34: 481-491, 2013
145. Rischin D, Peters LJ, O'Sullivan B, Giralt J, Fisher R, Yuen K, Trotti A, Bernier J, Bourhis J, Ringash J, Henke M, and Kenny L. Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): A phase III trial of the Trans-Tasman Radiation Oncology Group. J Clin Oncol 28: 2989-2995, 2010
146. Rothe F, Ignatiadis M, Chaboteaux C, Haibe-Kains B, Kheddoumi NM, Majjaj S, Badran B, Fayyad-Kazan H, Desmedt C, Harris AL, Piccart M, and Sotiriou C. Global microRNA expression profiling identifies MiR-210 associated with tumor proliferation, invasion and poor clinical outcome in breast cancer. PLoS One 6: E20980, 2011
147. Ruan K, Song G, and Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem 107: 1053-1062, 2009
148. Sarkar J, Gou D, Turaka P, Viktorova E, Ramchandran R, and Raj JU. MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration. Am J Physiol Lung Cell Mol Physiol 299: L861-L871, 2010
149. Satzger I, Mattern A, Kuettler U, Weinspach D, Voelker B, Kapp A, Gutzmer R. MicroRNA-15b represents an independent prognostic parameter and is correlated with tumor cell proliferation and apoptosis in malignant melanoma. Int J Cancer 126: 2553-62, 2010
150. Sayed D, He M, Hong C, Gao S, Rane S, Yang Z, and Abdellatif M. MicroRNA-21 is a downstream effector of AKT that mediates its antiapoptotic effects via suppression of Fas ligand. J Biol Chem 285: 20281-20290, 2010
151. Schindl M, Schoppmann SF, Samonigg H, Hausmaninger H, Kwasny W, Gnant M, Jakesz R, Kubista E, Birner P, and Oberhuber G. Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res 8: 1831-1837, 2002
152. Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, and Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115: 199-208, 2003
153. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, and Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 455: 58-63, 2008
154. Semenza GL. Angiogenesis ischemic and neoplastic disorders. Annu Rev Med 54: 17-28, 2003
155. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29: 625-634, 2010
156. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell 148: 399-408, 2012
157. Shen J, Xia W, Khotskaya YB, Huo L, Nakanishi K, Lim SO, Du Y, Wang Y, Chang WC, Chen CH, Hsu JL, Wu Y, Lam YC, James BP, Liu X, Liu CG, Patel DJ, and Hung MC. EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature 497: 383-387, 2013
158. Shinohara A and Ogawa T. Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature 391: 404-407, 1998
159. Simone NL, Soule BP, Ly D, Saleh AD, Savage JE, Degraff W, Cook J, Harris CC, Gius D, and Mitchell JB. Ionizing radiation-induced oxidative stress alters miRNA expression. PLoS One 4: E6377, 2009
160. Stenvang J, Silahtaroglu AN, Lindow M, Elmen J, and Kauppinen S. The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Semin Cancer Biol 18: 89-102, 2008
161. Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y, Goto H, and Takahashi T. Identification of hypoxiainducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res 68: 5540-5545, 2008
162. Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, and Harris AL. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-Associated macrophages. Am J Pathol 157: 411-421, 2000
163. Taylor DD and Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110: 13-21, 2008
164. Tetzlaff MT, Liu A, Xu X, Master SR, Baldwin DA, Tobias JW, Livolsi VA, and Baloch ZW. Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues. Endocr Pathol 18: 163-173, 2007
165. Tombol Z, Szabo PM, Molnar V, Wiener Z, Tolgyesi G, Horanyi J, Riesz P, Reismann P, Patocs A, Liko I, Gaillard RC, Falus A, Racz K, Igaz P. Integrative molecular bioinformatics study of human adrenocortical tumors: Micro-RNA, tissue-specific target prediction, and pathway analysis. Endocr Relat Cancer 16: 895-906, 2009
166. Tong WH and Rouault TA. Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab 3: 199-210, 2006
167. Toyama T, Kondo N, Endo Y, Sugiura H, Yoshimoto N, Iwasa M, Takahashi S, Fujii Y, and Yamashita H. 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: 256-263, 2012
168. Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O'Brien C, and Rose B. MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun 358: 12-17, 2007
169. Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, and Tsujimoto G.MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem 286: 420-428, 2011
170. Vaksman O, Stavnes HT, Kaern J, Trope CG, Davidson B, Reich R. miRNA profiling along tumour progression in ovarian carcinoma. J Cell Mol Med 15: 1593-602, 2011
171. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, and Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9: 654-659, 2007
172. Valencia-Sanchez MA, Liu J, Hannon GJ, and Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20: 515-524, 2006
173. Ventura A and Jacks T. MicroRNAs and cancer: Short RNAs go a long way. Cell 136: 586-591, 2009
174. Voellenkle C, Rooij J, Guffanti A, Brini E, Fasanaro P, Isaia E, Croft L, David M, Capogrossi MC, Moles A, Felsani A, and Martelli F. Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs. RNA 18: 472-484, 2012
175. Volinia S, Calin G, Liu C, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt R, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris C, and Croce C. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103: 2257-2261, 2006
176. Vordermark D, Katzer A, Baier K, Kraft P, and Flentje M. Cell type-specific association of hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein accumulation and radiobiologic tumor hypoxia. Int J Radiat Oncol Biol Phys 58: 1242-1250, 2004
177. Wan G, Mathur R, Hu X, Zhang X, and Lu X. miRNA response to DNA damage. Trends Biochem Sci 36: 478-484, 2011
178. Wang GL, Jiang BH, Rue EA, and Semenza GL. Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92: 5510-5514, 1995
179. Wang GL and Semenza GL. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A 90: 4304-4308, 1993
180. Wang GL and Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270: 1230-1237, 1995
181. Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, and Sen S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res 2: 807-813, 2009
182. Wang S and Olson EN. AngiomiRs-key regulators of angiogenesis. Curr Opin Genet Dev 19: 205-211, 2009
183. Weber JA, Baxter DH, Zhang S, Huang DY, How Huang K, Jen Lee M, Galas DJ, and Wang K. The microRNA spectrum in 12 body fluids. Clin Chem 56: 1733-1741, 2010
184. White NM, Bao TT, Grigull J, Youssef YM, Girgis A, Diamandis M, Fatoohi E, Metias M, Honey RJ, Stewart R, Pace KT, Bjarnason GA, and Yousef GM. miRNA profiling for clear cell renal cell carcinoma: Biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol 186: 1077-1083, 2011
185. Wilson WR and Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer 11: 393-410, 2011
186. Wu C, So J, Davis-Dusenbery BN, Qi HH, Bloch DB, Shi Y, Lagna G, and Hata A. Hypoxia potentiates microRNAmediated gene silencing through posttranslational modification of Argonaute2. Mol Cell Biol 31: 4760-4774, 2011
187. Wu F, Yang Z, and Li G. Role of specific microRNAs for endothelial function and angiogenesis. Biochem Biophys Res Commun 386: 549-553, 2009
188. Xing L, Todd NW, Yu L, Fang H, Jiang F. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers. Mod Pathol 23: 1157-64, 2010
189. Xu X, Jia R, Zhou Y, Song X, Wang J, Qian G, Ge S, and Fan X. Microarray-based analysis: Identification of hypoxiaregulated microRNAs in retinoblastoma cells. Int J Oncol 38: 1385-1393, 2011
190. Yamakuchi M, Lotterman CD, Bao C, Hruban RH, Karim B, Mendell JT, Huso D, and Lowenstein CJ. P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc Natl Acad Sci U S A 107: 6334-6339, 2010
191. Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, and Sun SH. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J 28: 2719-2732, 2009
192. 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, and Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9: 189-198, 2006
193. Yang W, Sun T, Cao J, Liu F, Tian Y, and Zhu W. Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp Cell Res 318: 944-954, 2012
194. This reference has been Deleted
195. Yang W, Wei J, Sun T, and Liu F. Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice. Radiat Oncol 8: 102, 2013
196. Yeh YM, Chuang CM, Chao KC, and Wang LH. Micro-RNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1alpha. Int J Cancer 133: 867-878, 2013
197. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, and Lee JT. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152: 727-742, 2013
198. 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. Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology 54: 2064-75, 2011
199. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, and Semenza GL. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHLdeficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11: 407-420, 2007
200. Zhang H, Pu J, Qi T, Qi M, Yang C, Li S, Huang K, Zheng L, and Tong Q. MicroRNA-145 inhibits the growth, invasion, metastasis and angiogenesis of neuroblastoma cells through targeting hypoxia-inducible factor 2 alpha. Oncogene [Epub ahead of print]; DOI: 10.1038/onc.2012.574, 2012
201. Zhang X, Wan G, Berger FG, He X, and Lu X. The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell 41: 371-383, 2011
202. Zhang Y, Fei M, Xue G, Zhou Q, Jia Y, Li L, Xin H, and Sun S. Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: New insights into molecular mechanisms for the disease. J Cell Mol Med 16: 249-259, 2012
203. 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, and Grandori C. MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle 8: 2756-2768, 2009
204. Zhao A, Li G, Peoch M, Genin C, and Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol 94: 115-120, 2013
205. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, and Simons JW. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59: 5830-5835, 1999
206. Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk AR, Ryan HE, Johnson RS, Jefferson AB, Stokoe D, and Giaccia AJ. Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 14: 391-396, 2000