Hypoxia: A master regulator of microRNA biogenesis and activity

Free Radical Biology and Medicine

Volumn 64, Issue , 2013, Pages 20-30

  Nallamshetty, Shriram ^a,b   Chan, Stephen Y ^a   Loscalzo, Joseph ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Free radicals; HIF; Hypoxamir; Hypoxia; MicroRNA

Indexed keywords

FAS LIGAND; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; HYPOXIA INDUCIBLE FACTOR 3ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MICRORNA; MICRORNA 122; MICRORNA 125B; MICRORNA 146A; MICRORNA 155; MICRORNA 15B; MICRORNA 192; MICRORNA 200B; MICRORNA 205; MICRORNA 20B; MICRORNA 21; MICRORNA 210; MICRORNA 24; MICRORNA 26A; MICRORNA 34A; MICRORNA 373; MICRORNA 451; MICRORNA 474; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PROTEIN KINASE B BETA; PROTEIN P53; RNA; THROMBIN RECEPTOR ACTIVATING PEPTIDE 6; UNCLASSIFIED DRUG; VON HIPPEL LINDAU PROTEIN;

ANGIOGENESIS; APOPTOSIS; AUTOPHAGY; BINDING SITE; BIOGENESIS; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CELL ENERGY; CELL METABOLISM; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; DNA REPAIR; ENDOPLASMIC RETICULUM STRESS; ENERGY CONSERVATION; EPITHELIAL MESENCHYMAL TRANSITION; ERYTHROPOIESIS; GENE SILENCING; GLYCOLYSIS; HUMAN; HYDROXYLATION; HYPOXIA; MATURATION; MITOCHONDRIAL RESPIRATION; NEGATIVE FEEDBACK; NONHUMAN; OXYGEN CONSUMPTION; OXYGEN TENSION; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; REGULATORY MECHANISM; REVIEW; RNA DEGRADATION; RNA PROCESSING; TRANSCRIPTION INITIATION; TRANSCRIPTION INITIATION SITE; UBIQUITINATION; UNFOLDED PROTEIN RESPONSE;

3′ UNTRANSLATED REGION; 3′UTR; AGO2; ARGONAUTE 2; CCN5; CHIP; CHROMATIN IMMUNOPRECIPITATION; CUL2; CULLIN2; CYSTEINE-RICH 61/CONNECTIVE TISSUE GROWTH FACTOR/NEPHROBLASTOMA OVEREXPRESSED 5; DGCR8; DI GEORGE SYNDROME CRITICAL REGION 8; DMNT; DNA METHYLTRANSFERASE; E2F TRANSCRIPTION FACTOR 3; E2F3; FREE RADICALS; HIF; HRE; HUMAN UMBILICAL VEIN ENDOTHELIAL CELL; HUVEC; HYPOXAMIR; HYPOXIA; HYPOXIA-INDUCIBLE FACTOR; HYPOXIA-RESPONSIVE ELEMENT; MAMMALIAN TARGET OF RAPAMYCIN; MICRORNA; MIRISC; MIRNA; MIRNA-INDUCED SILENCING COMPLEX; MTOR; NF-ΚB; NUCLEAR FACTOR-ΚB; ODD; OXYGEN-DEPENDENT DOMAIN; POSTTRANSLATIONAL MODIFICATION; PRE-MIRNA; PRECURSOR MIRNA; PRI-MIRNA; PRIMARY MICRORNA; PTM; REACTIVE OXYGEN SPECIES; ROS; TF; TNF RECEPTOR-ASSOCIATED FACTOR 6; TRAF6; TRANSCRIPTION FACTOR; TWIST-RELATED PROTEIN 1; TWIST1; UNFOLDED PROTEIN RESPONSE; UPR; VHL; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; ANOXIA; APOPTOSIS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HUMANS; MICRORNAS; OXYGEN; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84885188064     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2013.05.022     Document Type: Review

References (123)

1. Crosby, M. E.; Kulshreshtha, R.; Ivan, M.; Glazer, P. M. MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 69:1221-1229; 2009.
2. Kulshreshtha, R.; Ferracin, M.; Wojcik, S. E.; Garzon, R.; Alder, H.; Agosto-Perez, F. J.; Davuluri, R.; Liu, C. G.; Croce, C. M.; Negrini, M.; Calin, G. A.; Ivan, M. A microRNA signature of hypoxia. Mol. Cell. Biol. 27:1859-1867; 2007.
3. Pocock, R. Decoding the microRNA response to hypoxia. Pflugers Arch. 461:307-315; 2011.
4. Bentwich, I.; Avniel, A.; Karov, Y.; Aharonov, R.; Gilad, S.; Barad, O.; Barzilai, A.; Einat, P.; Einav, U.; Meiri, E.; Sharon, E.; Spector, Y.; Bentwich, Z. Identification of hundreds of conserved and nonconserved human microRNAs. Nat. Genet. 37:766-770; 2005. (Pubitemid 41754896)
5. Berezikov, E.; Cuppen, E.; Plasterk, R. H. Approaches to microRNA discovery. Nat. Genet 38(Suppl):S2-7; 2006.
6. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281-297; 2004.
7. Loscalzo, J. The cellular response to hypoxia: tuning the system with microRNAs. J. Clin. Invest. 120:3815-3817; 2010.
8. Chan, S. Y.; Zhang, Y. Y.; Hemann, C.; Mahoney, C. E.; Zweier, J. L.; 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.
9. Favaro, E.; Ramachandran, A.; McCormick, R.; Gee, H.; Blancher, C.; Crosby, M.; Devlin, C.; Blick, C.; Buffa, F.; Li, J. L.; Vojnovic, B.; Pires das Neves, R.; Glazer, P.; Iborra, F.; Ivan, M.; Ragoussis, J.; Harris, A. L. 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; 2010e103455; 2010.
10. Ghosh, G.; Subramanian, I. V.; Adhikari, N.; Zhang, X.; Joshi, H. P.; Basi, D.; Chandrashekhar, Y. S.; Hall, J. L.; Roy, S.; Zeng, Y.; Ramakrishnan, S. Hypoxiainduced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J. Clin. Invest. 120:4141-4154; 2010.
11. Majmundar, A. J.; Wong, W. J.; Simon, M. C. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell 40:294-309; 2010.
12. Semenza, G. L. Hypoxia-inducible factors in physiology and medicine. Cell 148:399-408; 2012.
13. Sermeus, A.; Michiels, C. Reciprocal influence of the p53 and the hypoxic pathways. Cell Death Dis. 2; 2011e1642; 2011.
14. An, W. G.; Kanekal, M.; Simon, M. C.; Maltepe, E.; Blagosklonny, M. V.; Neckers, L. M. Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature 392:405-408; 1998.
15. Carmeliet, P.; Dor, Y.; Herbert, J. M.; Fukumura, D.; Brusselmans, K.; Dewerchin, M.; Neeman, M.; Bono, F.; Abramovitch, R.; Maxwell, P.; Koch, C. J.; Ratcliffe, P.; Moons, L.; Jain, R. K.; Collen, D.; Keshert, E. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485-490; 1998. (Pubitemid 28373960)
16. Hammond, E. M.; Denko, N. C.; Dorie, M. J.; Abraham, R. T.; Giaccia, A. J. Hypoxia links ATR and p53 through replication arrest. Mol. Cell. Biol. 22:1834-1843; 2002. (Pubitemid 34174999)
17. Sarbassov, D. D.; Ali, S. M.; Sabatini, D. M. Growing roles for the mTOR pathway. Curr. Opin. Cell Biol. 17: 596-603; 2005. (Pubitemid 41540408)
18. Sofer, A.; Lei, K.; Johannessen, C. M.; Ellisen, L. W. Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol. Cell. Biol. 25:5834-5845; 2005. (Pubitemid 40946541)
19. Koritzinsky, M.; Magagnin, M. G.; van den Beucken, T.; Seigneuric, R.; Savelkouls, K.; Dostie, J.; Pyronnet, S.; Kaufman, R. J.; Weppler, S. A.; Voncken, J. W.; Lambin, P.; Koumenis, C.; Sonenberg, N.; Wouters, B. G. Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control. EMBO J. 25:1114-1125; 2006. (Pubitemid 43372124)
20. Zhao, L.; Ackerman, S. L. Endoplasmic reticulum stress in health and disease. Curr. Opin. Cell Biol. 18: 444-452; 2006. (Pubitemid 44026518)
21. Xu, C.; Bailly-Maitre, B.; Reed, J. C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest. 115: 2656-2664; 2005. (Pubitemid 41434389)
22. Baek, D.; Villen, J.; Shin, C.; Camargo, F. D.; Gygi, S. P.; Bartel, D. P. The impact of microRNAs on protein output. Nature 455:64-71; 2008.
23. Selbach, M.; Schwanhausser, B.; Thierfelder, N.; Fang, Z.; Khanin, R.; Rajewsky, N. Widespread changes in protein synthesis induced by micro-RNAs. Nature 455:58-63; 2008.
24. Greer, S. N.; Metcalf, J. L.; Wang, Y.; Ohh, M. The updated biology of hypoxia-inducible factor. EMBO J. 31:2448-2460; 2012.
25. Kelly, T. J.; Souza, A. L.; Clish, C. B.; Puigserver, P. 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 31:2696-2706; 2011.
26. Cascio, S.; D'Andrea, A.; Ferla, R.; Surmacz, E.; Gulotta, E.; Amodeo, V.; Bazan, V.; Gebbia, N.; 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.
27. Rane, S.; He, M.; Sayed, D.; Vashistha, H.; Malhotra, A.; Sadoshima, J.; Vatner, D. E.; Vatner, S. F.; Abdellatif, M. Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ. Res. 104:879-886; 2009.
28. Bruning, U.; Cerone, L.; Neufeld, Z.; Fitzpatrick, S. F.; Cheong, A.; Scholz, C. C.; Simpson, D. A.; Leonard, M. O.; Tambuwala, M. M.; Cummins, E. P.; Taylor, C. T. MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol. Cell. Biol. 31:4087-4096; 2011.
29. Giannakakis, A.; Sandaltzopoulos, R.; Greshock, J.; Liang, S.; Huang, J.; Hasegawa, K.; Li, C.; O'Brien-Jenkins, A.; Katsaros, D.; Weber, B. L.; Simon, C.; Coukos, G.; 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. (Pubitemid 351590433)
30. Taganov, K. D.; Boldin, M. P.; Chang, K. J.; Baltimore, D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA 103:12481-12486; 2006. (Pubitemid 44267285)
31. Zhang, L.; Dong, L. Y.; Li, Y. J.; Hong, Z.; Wei, W. S. The microRNA miR-181c controls microglia-mediated neuronal apoptosis by suppressing tumor necrosis factor. J. Neuroinflammation 9:211; 2012.
32. Hua, Z.; Lv, Q.; Ye, W.; Wong, C. K.; Cai, G.; Gu, D.; Ji, Y.; Zhao, C.; Wang, J.; Yang, B. B.; Zhang, Y. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1:e116; 2006.
33. Lee, Y.; Kim, M.; Han, J.; Yeom, K. H.; Lee, S.; Baek, S. H.; Kim, V. N. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23:4051-4060; 2004. (Pubitemid 39472426)
34. Borchert, G. M.; Lanier, W.; Davidson, B. L. RNA polymerase III transcribes human microRNAs. Nat. Struct. Mol. Biol. 13:1097-1101; 2006. (Pubitemid 44885920)
35. Cai, X.; Hagedorn, C. H.; Cullen, B. R. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10:1957-1966; 2004. (Pubitemid 39557833)
36. Lee, Y.; Ahn, C.; Han, J.; Choi, H.; Kim, J.; Yim, J.; Lee, J.; Provost, P.; Radmark, O.; Kim, S.; Kim, V. N. The nuclear RNase III drosha initiates microRNA processing. Nature 425:415-419; 2003. (Pubitemid 37187272)
37. Gregory, R. I.; Yan, K. P.; Amuthan, G.; Chendrimada, T.; Doratotaj, B.; Cooch, N.; Shiekhattar, R. The microprocessor complex mediates the genesis of micro-RNAs. Nature 432:235-240; 2004. (Pubitemid 39545855)
38. Denli, A. M.; Tops, B. B.; Plasterk, R. H.; Ketting, R. F.; Hannon, G. J. Processing of primary microRNAs by the microprocessor complex. Nature 432:231-235; 2004. (Pubitemid 39545854)
39. Bohnsack, M. T.; Czaplinski, K.; Gorlich, D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10:185-191; 2004. (Pubitemid 38129823)
40. Lee, Y.; Jeon, K.; Lee, J. T.; Kim, S.; Kim, V. N. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 21:4663-4670; 2002. (Pubitemid 34984353)
41. O'Toole, A. S.; Miller, S.; Haines, N.; Zink, M. C.; Serra, M. J. Comprehensive thermodynamic analysis of 3′ double-nucleotide overhangs neighboring Watson-Crick terminal base pairs. Nucleic Acids Res. 34:3338-3344; 2006.
42. Guo, H.; Ingolia, N. T.; Weissman, J. S.; Bartel, D. P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835-840; 2010.
43. Zhang, Y.; Fei, M.; Xue, G.; Zhou, Q.; Jia, Y.; Li, L.; Xin, H.; 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.
44. Dinger, M. E.; Mercer, T. R.; Mattick, J. S. RNAs as extracellular signaling molecules. J. Mol. Endocrinol. 40:151-159; 2008. (Pubitemid 351586824)
45. Zhu, H.; Fan, G. C. Extracellular/circulating microRNAs and their potential role in cardiovascular disease. Am. J. Cardiovasc. Dis 1:138-149; 2011.
46. Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285:17442-17452; 2010.
47. Donker, R. B.; Mouillet, J. F.; Nelson, D. M.; Sadovsky, Y. The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts. Mol. Hum. Reprod. 13:273-279; 2007. (Pubitemid 46554745)
48. Guimbellot, J. S.; Erickson, S. W.; Mehta, T.; Wen, H.; Page, G. P.; Sorscher, E. J.; Hong, J. S. Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis. BMC Med. Genomics 2:15; 2009.
49. Voellenkle, C.; Rooij, J.; Guffanti, A.; Brini, E.; Fasanaro, P.; Isaia, E.; Croft, L.; David, M.; Capogrossi, M. C.; Moles, A.; Felsani, A.; Martelli, F. Deepsequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs. RNA 18:472-484; 2012.
50. Rodriguez, A.; Griffiths-Jones, S.; Ashurst, J. L.; Bradley, A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 14:1902-1910; 2004. (Pubitemid 39386503)
51. Corcoran, D. L.; Pandit, K. V.; Gordon, B.; Bhattacharjee, A.; Kaminski, N.; Benos, P. V. Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS One 4; 2009e52794; 2009.
52. Ozsolak, F.; Poling, L. L.; Wang, Z.; Liu, H.; Liu, X. S.; Roeder, R. G.; Zhang, X.; Song, J. S.; Fisher, D. E. Chromatin structure analyses identify miRNA promoters. Genes Dev. 22:3172-3183; 2008.
53. Monteys, A. M.; Spengler, R. M.; Wan, J.; Tecedor, L.; Lennox, K. A.; Xing, Y.; Davidson, B. L. Structure and activity of putative intronic miRNA promoters. RNA 16:495-505; 2010.
54. Wang, J.; Lu, M.; Qiu, C.; Cui, Q. TransmiR: a transcription factor-microRNA regulation database. Nucleic Acids Res. 38:D119-22; 2010.
55. Croft, L.; Szklarczyk, D.; Jensen, L. J.; Gorodkin, J. Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs. BMC. Syst. Biol. 6:90; 2012.
56. Cummins, E. P.; Taylor, C. T. Hypoxia-responsive transcription factors. Pflugers Arch. 450:363-371; 2005. (Pubitemid 41380694)
57. Kulshreshtha, R.; Ferracin, M.; Negrini, M.; Calin, G. A.; Davuluri, R. V.; Ivan, M. Regulation of microRNA expression: the hypoxic component. Cell Cycle 6:1426-1431; 2007.
58. Camps, C.; Buffa, F. M.; Colella, S.; Moore, J.; Sotiriou, C.; Sheldon, H.; Harris, A. L.; Gleadle, J. M.; 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. (Pubitemid 351413913)
59. Huang, X.; Ding, L.; Bennewith, K. L.; Tong, R. T.; Welford, S. M.; Ang, K. K.; Story, M.; Le, Q. T.; Giaccia, A. J. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol. Cell 35:856-867; 2009.
60. Chan, S. Y.; Loscalzo, J. MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle 9:1072-1083; 2010.
61. Fasanaro, P.; Greco, S.; Lorenzi, M.; Pescatori, M.; Brioschi, M.; Kulshreshtha, R.; Banfi, C.; Stubbs, A.; Calin, G. A.; Ivan, M.; Capogrossi, M. C.; Martelli, F. An integrated approach for experimental target identification of hypoxia-induced miR-210. J. Biol. Chem. 284:35134-35143; 2009.
62. Chan, Y. C.; Banerjee, J.; Choi, S. Y.; Sen, C. K. miR-210: the master hypoxamir. Microcirculation 19:215-223; 2012.
63. Gorospe, M.; Tominaga, K.; Wu, X.; Fahling, M.; Ivan, M. Post-transcriptional control of the hypoxic response by RNA-binding proteins and MicroRNAs. Front. Mol. Neurosci. 4:7; 2011.
64. Parikh, V. N.; Jin, R. C.; Rabello, S.; Gulbahce, N.; White, K.; Hale, A.; Cottrill, K. A.; Shaik, R. S.; Waxman, A. B.; Zhang, Y. Y.; Maron, B. A.; Hartner, J. C.; Fujiwara, Y.; Orkin, S. H.; Haley, K. J.; Barabasi, A. L.; Loscalzo, J.; Chan, S. Y. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation 125:1520-1532; 2012.
65. Polytarchou, C.; Iliopoulos, D.; Hatziapostolou, M.; Kottakis, F.; Maroulakou, I.; Struhl, K.; Tsichlis, P. N. Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res. 71:4720-4731; 2011.
66. Haque, I.; Banerjee, S.; Mehta, S.; De, A.; Majumder, M.; Mayo, M. S.; Kambhampati, S.; Campbell, D. R.; Banerjee, S. K. Cysteine-rich 61-connective tissue growth factor-nephroblastoma-overexpressed 5 (CCN5)/Wnt-1-induced signaling protein-2 (WISP-2) regulates microRNA-10b via hypoxiainducible factor-1alpha-TWIST signaling networks in human breast cancer cells. J. Biol. Chem. 286:43475-43485; 2011.
67. Preis, M.; Gardner, T. B.; Gordon, S. R.; Pipas, J. M.; Mackenzie, T. A.; Klein, E. E.; Longnecker, D. S.; Gutmann, E. J.; Sempere, L. F.; Korc, M. MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin. Cancer Res. 17: 5812-5821; 2011.
68. Hermeking, H. The miR-34 family in cancer and apoptosis. Cell Death Differ 17: 193-199; 2010.
69. Klein, U.; Lia, M.; Crespo, M.; Siegel, R.; Shen, Q.; Mo, T.; Ambesi-Impiombato, A.; Califano, A.; Migliazza, A.; Bhagat, G.; Dalla-Favera, R. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 17: 28-40; 2010.
70. Chang, C. J.; Chao, C. H.; Xia, W.; Yang, J. Y.; Xiong, Y.; Li, C. W.; Yu, W. H.; Rehman, S. K.; Hsu, J. L.; Lee, H. H.; Liu, M.; Chen, C. T.; Yu, D.; Hung, M. C. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat. Cell Biol. 13:317-323; 2011.
71. Kim, T.; Veronese, A.; Pichiorri, F.; Lee, T. J.; Jeon, Y. J.; Volinia, S.; Pineau, P.; Marchio, A.; Palatini, J.; Suh, S. S.; Alder, H.; Liu, C. G.; Dejean, A.; Croce, C. M. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J. Exp. Med. 208:875-883; 2011.
72. Hermeking, H. MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat. Rev. Cancer 12:613-626; 2012.
73. Mutharasan, R. K.; Nagpal, V.; Ichikawa, Y.; 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:H1519-1530; 2011.
74. Boldin, M. P.; Baltimore, D. MicroRNAs, new effectors and regulators of NF-kappaB. Immunol. Rev. 246:205-220; 2012.
75. Boldin, M. P.; Taganov, K. D.; Rao, D. S.; Yang, L.; Zhao, J. L.; Kalwani, M.; Garcia-Flores, Y.; Luong, M.; Devrekanli, A.; Xu, J.; Sun, G.; Tay, J.; Linsley, P. S.; Baltimore, D. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J. Exp. Med. 208:1189-1201; 2011.
76. Vigorito, E.; Perks, K. L.; Abreu-Goodger, C.; Bunting, S.; Xiang, Z.; Kohlhaas, S.; Das, P. P.; Miska, E. A.; Rodriguez, A.; Bradley, A.; Smith, K. G.; Rada, C.; Enright, A. J.; Toellner, K. M.; Maclennan, I. C.; Turner, M. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27:847-859; 2007. (Pubitemid 350258623)
77. Sheedy, F. J.; Palsson-McDermott, E.; Hennessy, E. J.; Martin, C.; O'Leary, J. J.; Ruan, Q.; Johnson, D. S.; Chen, Y.; O'Neill, L. A. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat. Immunol. 11: 141-147; 2010.
78. Garzon, R.; Liu, S.; Fabbri, M.; Liu, Z.; Heaphy, C. E.; Callegari, E.; Schwind, S.; Pang, J.; Yu, J.; Muthusamy, N.; Havelange, V.; Volinia, S.; Blum, W.; Rush, L. J.; Perrotti, D.; Andreeff, M.; Bloomfield, C. D.; Byrd, J. C.; Chan, K.; Wu, L. C.; Croce, C. M.; Marcucci, G. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113: 6411-6418; 2009.
79. Lujambio, A.; Portela, A.; Liz, J.; Melo, S. A.; Rossi, S.; Spizzo, R.; Croce, C. M.; Calin, G. A.; Esteller, M. CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene 29:6390-6401; 2010.
80. Xiong, L.; Wang, F.; Huang, X.; Liu, Z. H.; Zhao, T.; Wu, L. Y.; Wu, K.; Ding, X.; Liu, S.; Wu, Y.; Zhao, Y.; Zhu, L. L.; Fan, M. DNA demethylation regulates the expression of miR-210 in neural progenitor cells subjected to hypoxia. FEBS J. 279:4318-4326; 2012.
81. Caruso, P.; MacLean, M. R.; Khanin, R.; McClure, J.; Soon, E.; Southgate, M.; MacDonald, R. A.; Greig, J. A.; Robertson, K. E.; Masson, R.; Denby, L.; Dempsie, Y.; Long, L.; Morrell, N. W.; Baker, A. H. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler. Thromb. Vasc. Biol. 30:716-723; 2010.
82. Ho, J. J.; Metcalf, J. L.; Yan, M. S.; Turgeon, P. J.; Wang, J. J.; Chalsev, M.; Petruzziello-Pellegrini, T. N.; Tsui, A. K.; He, J. Z.; Dhamko, H.; Man, H. S.; Robb, G. B.; Teh, B. T.; Ohh, M.; Marsden, P. A. Functional importance of dicer protein in the adaptive cellular response to hypoxia. J. Biol. Chem. 287:29003-29020; 2012.
83. Wu, C.; So, J.; Davis-Dusenbery, B. N.; Qi, H. H.; Bloch, D. B.; Shi, Y.; Lagna, G.; Hata, A. Hypoxia potentiates microRNA-mediated gene silencing through posttranslational modification of Argonaute2. Mol. Cell. Biol. 31:4760-4774; 2011.
84. Eltzschig, H. K.; Abdulla, P.; Hoffman, E.; Hamilton, K. E.; Daniels, D.; Schonfeld, C.; Loffler, M.; Reyes, G.; Duszenko, M.; Karhausen, J.; Robinson, A.; Westerman, K. A.; Coe, I. R.; Colgan, S. P. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J. Exp. Med. 202:1493-1505; 2005. (Pubitemid 41746596)
85. Morote-Garcia, J. C.; Rosenberger, P.; Kuhlicke, J.; Eltzschig, H. K. HIF-1-dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak. Blood 111: 5571-5580; 2008.
86. Ibla, J. C.; Khoury, J.; Kong, T.; Robinson, A.; Colgan, S. P. Transcriptional repression of na-K-2Cl cotransporter NKCC1 by hypoxia-inducible factor-1. Am. J. Physiol. Cell. Physiol 291:C282-C289; 2006. (Pubitemid 44148151)
87. Weigand, J. E.; Boeckel, J. N.; Gellert, P.; Dimmeler, S. Hypoxia-induced alternative splicing in endothelial cells. PLoS One. e42697; 2012.
88. Yan, K.; Liu, P.; Wu, C. A.; Yang, G. D.; Xu, R.; Guo, Q. H.; Huang, J. G.; Zheng, C. C. Stress-induced alternative splicing provides a mechanism for the regulation of microRNA processing in Arabidopsis thaliana. Mol. Cell 48:421-531; 2012.
89. Nevo-Caspi, Y.; Amariglio, N.; Rechavi, G.; Paret, G.; A-to-I, R. N. A. editing is induced upon hypoxia. Shock 35:585-589; 2011.
90. Choudhury, Y.; Tay, F. C.; Lam, D. H.; Sandanaraj, E.; Tang, C.; Ang, B. T.; Wang, S. Attenuated adenosine-to-inosine editing of microRNA-376an promotes invasiveness of glioblastoma cells. J. Clin. Invest. 122:4059-4076; 2012.
91. Kawahara, Y.; Zinshteyn, B.; Sethupathy, P.; Iizasa, H.; Hatzigeorgiou, A. G.; Nishikura, K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315:1137-1140; 2007. (Pubitemid 46328026)
92. Yu, Z.; Hecht, N. B. The DNA/RNA-binding protein, translin, binds micro-RNA122a and increases its in vivo stability. J. Androl. 29:572-579; 2008.
93. Wang, J.; Haubrock, M.; Cao, K. M.; Hua, X.; Zhang, C. Y.; Wingender, E.; Li, J. Regulatory coordination of clustered microRNAs based on microRNA-transcription factor regulatory network. BMC. Syst. Biol. 5:199; 2011.
94. Piriyapongsa, J.; Jordan, I. K.; Conley, A. B.; Ronan, T.; Smalheiser, N. R. Transcription factor binding sites are highly enriched within microRNA precursor sequences. Biol. Direct 6:61; 2011.
95. Weir, E. K.; Archer, S. L. The role of redox changes in oxygen sensing. Respir. Physiol. Neurobiol. 174: 182-191; 2010.
96. Venkataraman, S.; Alimova, I.; Fan, R.; Harris, P.; Foreman, N.; Vibhakar, R. MicroRNA 128a increases intracellular ROS level by targeting bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS One 5:e10748; 2010.
97. Zhang, X.; Ng, W. L.; Wang, P.; Tian, L.; Werner, E.; Wang, H.; Doetsch, P.; Wang, Y. MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFalpha. Cancer Res. 72:4707-4713; 2012.
98. Xu, X.; Jia, R.; Zhou, Y.; Song, X.; Wang, J.; Qian, G.; Ge, S.; Fan, X. Microarray-based analysis: identification of hypoxia-regulated microRNAs in retinoblas-toma cells. Int. J. Oncol. 38:1385-1393; 2011.
99. Thulasingam, S.; Massilamany, C.; Gangaplara, A.; Dai, H.; Yarbaeva, S.; Subramaniam, S.; Riethoven, J. J.; Eudy, J.; Lou, M.; Reddy, J. miR-27bn, an oxidative stress-responsive microRNA modulates nuclear factor-βB pathway in RAW 264.7 cells. Mol. Cell. Biochem. 352:181-188; 2011.
100. 2 sensing. J. Biol. Chem. 275:25130-25138; 2000.
101. Schroedl, C.; McClintock, D. S.; Budinger, G. R.; Chandel, N. S. Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Am. J. Physiol. Lung Cell. Mol. Physiol 283:L922-L931; 2002. (Pubitemid 35204884)
102. Bonello, S.; Zahringer, C.; BelAiba, R. S.; Djordjevic, T.; Hess, J.; Michiels, C.; Kietzmann, T.; Gorlach, A. Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arterioscler. Thromb. Vasc. Biol. 27:755-761; 2007. (Pubitemid 46606703)
103. Wiesen, J. L.; Tomasi, T. B. Dicer is regulated by cellular stresses and interferons. Mol. Immunol. 46:1222-1228; 2009.
104. Hebert, C.; Norris, K.; Scheper, M. A.; Nikitakis, N.; Sauk, J. J. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol. Cancer 6:5; 2007.
105. Ghosh, A. K.; Shanafelt, T. D.; Cimmino, A.; Taccioli, C.; Volinia, S.; Liu, C. G.; Calin, G. A.; Croce, C. M.; Chan, D. A.; Giaccia, A. J.; Secreto, C.; Wellik, L. E.; Lee, Y. K.; Mukhopadhyay, D.; Kay, N. E. Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood 11 3: 5568-5574; 2009.
106. Gonsalves, C. S.; Kalra, V. K. Hypoxia-mediated expression of 5-lipoxygenase-activating protein involves HIF-1alpha and NF-kappaB and microRNAs 135a and 199a-5p. J. Immunol 184:3878-3888; 2010.
107. Jian, X.; Xiao-yan, Z.; Bin, H.; Yu-feng, Z.; Bo, K.; Zhi-nong, W.; Xin, N. MiR-204 regulate cardiomyocyte autophagy induced by hypoxia-reoxygenation through LC3-II. Int. J. Cardiol. 148:110-112; 2011.
108. Mouillet, J. F.; Chu, T.; Nelson, D. M.; Mishima, T.; Sadovsky, Y. MiR-205 silences MED1 in hypoxic primary human trophoblasts. FASEB J. 24:2030-2039; 2010.
109. Muth, M.; Hussein, K.; Jacobi, C.; Kreipe, H.; Bock, O. Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression. J. Transl. Med. 9:24; 2011.
110. Ye, Y.; Perez-Polo, J. R.; Qian, J.; Birnbaum, Y. The role of microRNA in modulating myocardial ischemia-reperfusion injury. Physiol. Genomics 43:534-542; 2011.
111. Saito, K.; Kondo, E.; Matsushita, M. MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6. Nucleic Acids Res 39:6086-6099; 2011.
112. Cheng, Y.; Zhu, P.; Yang, J.; Liu, X.; Dong, S.; Wang, X.; Chun, B.; Zhuang, J.; Zhang, C. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc. Res. 87:431-439; 2010.
113. Sarkar, J.; Gou, D.; Turaka, P.; Viktorova, E.; Ramchandran, R.; Raj, J. U. MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration. Am. J. Physiol. Lung Cell. Mol. Physiol 299:L861-71; 2010.
114. Sayed, D.; He, M.; Hong, C.; Gao, S.; Rane, S.; Yang, Z.; 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.
115. Suh, J. H.; Choi, E.; Cha, M. J.; Song, B. W.; Ham, O.; Lee, S. Y.; Yoon, C.; Lee, C. Y.; Park, J. H.; Lee, S. H.; Hwang, K. C. Up-regulation of miR-26a promotes apoptosis of hypoxic rat neonatal cardiomyocytes by repressing GSK-3beta protein expression. Biochem. Biophys. Res. Commun. 423:404-410; 2012.
116. Urbich, C.; Kaluza, D.; Fromel, T.; Knau, A.; Bennewitz, K.; Boon, R. A.; Bonauer, A.; Doebele, C.; Boeckel, J. N.; Hergenreider, E.; Zeiher, A. M.; Kroll, J.; Fleming, I.; Dimmeler, S. MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood 119: 1607-1616; 2012.
117. Xiao, J.; Zhu, X.; He, B.; Zhang, Y.; Kang, B.; Wang, Z.; Ni, X. MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J. Biomed. Sci. 18:35; 2011.
118. Puissegur, M. P.; Mazure, N. M.; Bertero, T.; Pradelli, L.; Grosso, S.; Robbe-Sermesant, K.; Maurin, T.; Lebrigand, K.; Cardinaud, B.; Hofman, V.; Fourre, S.; Magnone, V.; Ricci, J. E.; Pouyssegur, J.; Gounon, P.; Hofman, P.; Barbry, P.; 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.
119. Chen, Z.; Li, Y.; Zhang, H.; Huang, P.; Luthra, R. Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29:4362-4368; 2010.
120. Ivan, M.; Harris, A. L.; Martelli, F.; Kulshreshtha, R. Hypoxia response and microRNAs: no longer two separate worlds. J. Cell. Mol. Med. 12:1426-1431; 2008.
121. Du, R.; Sun, W.; Xia, L.; Zhao, A.; Yu, Y.; Zhao, L.; Wang, H.; Huang, C.; Sun, S. Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the notch signaling pathway in tubular epithelial cells. PLoS One 7; 2012e307717; 2012.
122. Yang, F.; Zhang, L.; Wang, F.; Wang, Y.; Huo, X. S.; Yin, Y. X.; Wang, Y. Q.; Zhang, L.; Sun, S. H. Modulation of the unfolded protein response is the core of microRNA-122-involved sensitivity to chemotherapy in hepatocellular carcinoma. Neoplasia 13:590-600; 2011.
123. Chan, Y. C.; Khanna, S.; Roy, S.; Sen, C. K. miR-200b targets ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J. Biol. Chem. 286:2047-2056; 2011.