Genetic Networks Lead and Follow Tumor Development: MicroRNA Regulation of Cell Cycle and Apoptosis in the p53 Pathways

BioMed Research International

Volumn 2014, Issue , 2014, Pages

  Otsuka, Kurataka ^a,b   Ochiya, Takahiro ^a  

^a NATIONAL CANCER CENTER RESEARCH INSTITUTE   (Japan)

^b KEWPIE CORPORATION   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA; MICRORNA 107; MICRORNA 125B; MICRORNA 145; MICRORNA 15A; MICRORNA 16 1; MICRORNA 17 92; MICRORNA 192; MICRORNA 200C; MICRORNA 215; MICRORNA 34; MICRORNA LET 7A; MICRORNA LET 7B; PROTEIN P53; UNCLASSIFIED DRUG; CELL CYCLE PROTEIN;

APOPTOSIS; ARTICLE; BIOGENESIS; CANCER CELL; CANCER INHIBITION; CANCER PREVENTION; CANCER THERAPY; CARCINOGENESIS; CELL CYCLE; CELL CYCLE ARREST; CELL CYCLE REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; GENE EXPRESSION; GENE FUNCTION; GENE TARGETING; GENETIC ANALYSIS; GENETIC REGULATION; HUMAN; NONHUMAN; PROMOTER REGION; REGULATORY MECHANISM; TRANSACTIVATION; TUMOR GROWTH; ANIMAL; BIOLOGICAL MODEL; GENETICS; NEOPLASM; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CARCINOGENESIS; CELL CYCLE; CELL CYCLE PROTEINS; HUMANS; MICRORNAS; MODELS, GENETIC; NEOPLASMS; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84919454311     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2014/749724     Document Type: Article

References (142)

1. G. A. Calin and C. M. Croce, "MicroRNA signatures in human cancers, " Nature Reviews Cancer, vol. 6, no. 11, pp. 857-866, 2006.
2. K. H. Vousden and D. P. Lane, "p53 in health and disease, " Nature ReviewsMolecular Cell Biology, vol. 8, no. 4, pp. 275-283, 2007.
3. S. Pelengaris, M. Khan, and G. Evan, "c-MYC: more than just a matter of life and death, " Nature Reviews Cancer, vol. 2, no. 10, pp. 764-776, 2002.
4. B. Vogelstein and K. W. Kinzler, "Cancer genes and the pathways they control, " Nature Medicine, vol. 10, no. 8, pp. 789-799, 2004.
5. M. Olivier, S. P. Hussain, C. C. de Fromentel, P. Hainaut, and C. C. Harris, "TP53 mutation spectra and load: a tool for generating hypotheses on the etiology of cancer, " IARC Scientific Publications, vol. 157, no. 6, pp. 247-270, 2004.
6. A. J. Levine, W. Hu, and Z. Feng, "The P53 pathway: what questions remain to be explored?" Cell Death and Differentiation, vol. 13, no. 6, pp. 1027-1036, 2006.
7. W. S. El-Deiry, T. Tokino, V. E. Velculescu et al., "WAF1, a potential mediator of p53 tumor suppression, " Cell, vol. 75, no. 4, pp. 817-825, 1993.
8. J. Yu, L. Zhang, P. M. Hwang, K. W. Kinzler, and B. Vogelstein, "PUMA induces the rapid apoptosis of colorectal cancer cells, " Molecular Cell, vol. 7, no. 3, pp. 673-682, 2001.
9. H. Hermeking, C. Lengauer, K. Polyak et al., "14-3-3σ is a p53-regulated inhibitor of G2/Mprogression, "Molecular Cell, vol. 1, no. 1, pp. 3-11, 1997.
10. K. H. Vousden and C. Prives, "Blinded by the light: the growing complexity of p53, " Cell, vol. 137, no. 3, pp. 413-431, 2009.
11. K. B. Spurgers, D. L. Gold, K. R. Coombes et al., "Identification of cell cycle regulatory genes as principal targets of p53-mediated transcriptional repression, " The Journal of Biological Chemistry, vol. 281, no. 35, pp. 25134-25141, 2006.
12. J. Lu, G. Getz, E. A. Miska et al., "MicroRNA expression profiles classify human cancers, " Nature, vol. 435, no. 7043, pp. 834-838, 2005.
13. A. Lujambio and S. W. Lowe, "The microcosmos of cancer, " Nature, vol. 482, no. 7385, pp. 347-355, 2012.
14. N. Raver-Shapira, E. Marciano, E. Meiri et al., "Transcriptional activation of miR-34a contributes to p53-mediated apoptosis, " Molecular Cell, vol. 26, no. 5, pp. 731-743, 2007.
15. T.-C. Chang, E. A. Wentzel, O. A. Kent et al., "Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis, " Molecular Cell, vol. 26, no. 5, pp. 745-752, 2007.
16. L. He, X. He, L. P. Lim et al., "A microRNA component of the p53 tumour suppressor network, " Nature, vol. 447, no. 7148, pp. 1130-1134, 2007.
17. V. Tarasov, P. Jung, B. Verdoodt et al., "Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest, " Cell Cycle, vol. 6, no. 13, pp. 1586-1593, 2007.
18. G. T. Bommer, I. Gerin, Y. Feng et al., "p53-mediated activation of miRNA34 candidate tumor-suppressor genes, " Current Biology, vol. 17, no. 15, pp. 1298-1307, 2007.
19. R. C. Lee, R. L. Feinbaum, and V. Ambros, "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14, " Cell, vol. 75, no. 5, pp. 843-854, 1993.
20. B. Wightman, I. Ha, and G. Ruvkun, "Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans, " Cell, vol. 75, no. 5, pp. 855-862, 1993.
21. B. J. Reinhart, F. J. Slack, M. Basson et al., "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans, " Nature, vol. 403, no. 6772, pp. 901-906, 2000.
22. B. P. Lewis, C. B. Burge, and D. P. Bartel, "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets, " Cell, vol. 120, no. 1, pp. 15-20, 2005.
23. A. Krek, D. Grun, M. N. Poy et al., "Combinatorial microRNA target predictions, " Nature Genetics, vol. 37, no. 5, pp. 495-500, 2005.
24. Y. Lee, M. Kim, J. J. Han et al., "MicroRNAgenes are transcribed by RNA polymerase II, " The EMBO Journal, vol. 23, no. 20, pp. 4051-4060, 2004.
25. G. M. Borchert, W. Lanier, and B. L. Davidson, "RNA polymerase III transcribes human microRNAs, " Nature Structural and Molecular Biology, vol. 13, no. 12, pp. 1097-1101, 2006.
26. V. N. Kim, "MicroRNA biogenesis: coordinated cropping and dicing, " Nature Reviews Molecular Cell Biology, vol. 6, no. 5, pp. 376-385, 2005.
27. Y. Lee, K. Jeon, J.-T. Lee, S. Kim, and V. N. Kim, "MicroRNA maturation: stepwise processing and subcellular localization, " The EMBO Journal, vol. 21, no. 17, pp. 4663-4670, 2002.
28. E. Lund, S. Guttinger, A. Calado, J. E. Dahlberg, and U. Kutay, "Nuclear export of microRNA precursors, " Science, vol. 303, no. 5654, pp. 95-98, 2004.
29. D. P. Bartel, "MicroRNAs: genomics, biogenesis, mechanism, and function, " Cell, vol. 116, no. 2, pp. 281-297, 2004.
30. V. N. Kim, "Small RNAs: classification, biogenesis, and function, " Molecules and Cells, vol. 19, no. 1, pp. 1-15, 2005.
31. L. P. Lim, N. C. Lau, P. Garrett-Engele et al., "Microarray analysis shows that some microRNAs downregulate large numbers oftarget mRNAs, " Nature, vol. 433, no. 7027, pp. 769-773, 2005.
32. S. Bagga, J. Bracht, S. Hunter et al., "Regulation by let-7 and lin miRNAs results in target mRNA degradation, " Cell, vol. 122, no. 4, pp. 553-563, 2005.
33. E. C. Lai, "Predicting and validating microRNA targets, " Genome Biology, vol. 5, no. 9, article 115, 2004.
34. L. Wu and J. G. Belasco, "Let me count the ways: mechanisms of gene regulation bymiRNAs and siRNAs, "Molecular Cell, vol. 29, no. 1, pp. 1-7, 2008.
35. A. Eulalio, E. Huntzinger, and E. Izaurralde, "Getting to the root of miRNA-mediated gene silencing, " Cell, vol. 132, no. 1, pp. 9-14, 2008.
36. R. W. Carthew and E. J. Sontheimer, "Origins and mechanisms of miRNAs and siRNAs, " Cell, vol. 136, no. 4, pp. 642-655, 2009.
37. L. A. Yates, C. J. Norbury, and R. J. C. Gilbert, "The long and short of microRNA, " Cell, vol. 153, no. 3, pp. 516-519, 2013.
38. Y. Haupt, R. Maya, A. Kazaz, andM. Oren, "Mdm2 promotes the rapid degradation of p53, " Nature, vol. 387, no. 6630, pp. 296-299, 1997.
39. M. H. G. Kubbutat, S. N. Jones, and K. H. Vousden, "Regulation of p53 stability by Mdm2, " Nature, vol. 387, no. 6630, pp. 299-303, 1997.
40. C. L. Brooks and W. Gu, "p53 ubiquitination: mdm2 and beyond, " Molecular Cell, vol. 21, no. 3, pp. 307-315, 2006.
41. L. Roger, G. Gadea, and P. Roux, "Control of cell migration: a tumour suppressor function for p53?" Biology of the Cell, vol. 98, no. 3, pp. 141-152, 2006.
42. J. G. Teodoro, A. E. Parker, X. Zhu, and M. R. Green, "p53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase, " Science, vol. 313, no. 5789, pp. 968-971, 2006.
43. M. R. Junttila and G. I. Evan, "P53-a Jack of all trades but master of none, " Nature Reviews Cancer, vol. 9, no. 11, pp. 821-829, 2009.
44. S. A. Gatz and L. Wiesmuller, "p53 in recombination and repair, " Cell Death and Differentiation, vol. 13, no. 6, pp. 1003-1016, 2006.
45. K. Bensaad and K. H. Vousden, "Savior and slayer: the two faces of p53, " Nature Medicine, vol. 11, no. 12, pp. 1278-1279, 2005.
46. K. Bensaad, A. Tsuruta, M. A. Selak et al., "TIGAR, a p53-inducible regulator of glycolysis and apoptosis, " Cell, vol. 126, no. 1, pp. 107-120, 2006.
47. S. Matoba, J.-G. Kang, W. D. Patino et al., "p53 regulates mitochondrial respiration, " Science, vol. 312, no. 5780, pp. 1650-1653, 2006.
48. F. Murray-Zmijewski, D. P. Lane, and J.-C. Bourdon, "p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress, " Cell Death and Differentiation, vol. 13, no. 6, pp. 962-972, 2006.
49. S. Cawley, S. Bekiranov, H. H. Ng et al., "Unbiasedmapping of transcription factor binding sites along human chromosomes and 22 points to widespread regulation of noncoding RNAs, " Cell, vol. 116, no. 4, pp. 499-509, 2004.
50. C.-L. Wei, Q. Wu, V. B. Vega et al., "A global map of p53 transcription-factor binding sites in the human genome, " Cell, vol. 124, no. 1, pp. 207-219, 2006.
51. H. Tazawa, N. Tsuchiya, M. Izumiya, and H. Nakagama, "Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells, " Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 39, pp. 15472-15477, 2007.
52. D. C. Corney, A. Flesken-Nikitin, A. K. Godwin, W. Wang, and A. Y. Nikitin, "MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesionindependent growth, " Cancer Research, vol. 67, no. 18, pp. 8433-8438, 2007.
53. H. Hermeking, "MicroRNAs in the p53 network: micromanagement of tumour suppression, " Nature Reviews Cancer, vol. 12, no. 9, pp. 613-626, 2012.
54. H. Hermeking, "The miR-34 family in cancer and apoptosis, " Cell Death & Differentiation, vol. 17, no. 2, pp. 193-199, 2010.
55. M. Yamakuchi, C. D. Lotterman, C. Bao et al., "P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis, " Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 14, pp. 6334-6339, 2010.
56. L. Bohlig, M. Friedrich, and K. Engeland, "P53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins, " Nucleic Acids Research, vol. 39, no. 2, pp. 440-453, 2011.
57. G. Martello, A. Rosato, F. Ferrari et al., "AmicroRNA targeting dicer for metastasis control, " Cell, vol. 141, no. 7, pp. 1195-1207, 2010.
58. M. Z. Michael, S. M. OConnor, N. G. van Holst Pellekaan, G. P. Young, and R. J. James, "Reduced accumulation of specific microRNAs in colorectal neoplasia, "MolecularCancer Research, vol. 1, no. 12, pp. 882-891, 2003.
59. M. V. Iorio, M. Ferracin, C.-G. Liu et al., "MicroRNA gene expression deregulation in human breast cancer, " Cancer Research, vol. 65, no. 16, pp. 7065-7070, 2005.
60. S. O. Suh, Y. Chen, M. S. Zaman et al., "MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer, " Carcinogenesis, vol. 32, no. 5, pp. 772-778, 2011.
61. G. A. Calin, C. Sevignani, C. D. Dumitru et al., "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 9, pp. 2999-3004, 2004.
62. M. Sachdeva, S. M. Zhu, F. T. Wu et al., "p53 represses c-Myc through induction of the tumor suppressor miR-145, " Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 9, pp. 3207-3212, 2009.
63. H. Zhu, U. Dougherty, V. Robinson et al., "EGFR signals downregulate tumor suppressors miR-143 and miR-145 in Western diet-promoted murine colon cancer: role of G1 regulators, " Molecular Cancer Research, vol. 9, no. 7, pp. 960-975, 2011.
64. A. Lujambio and M. Esteller, "CpG island hypermethylation of tumor suppressor microRNAs in human cancer, " Cell Cycle, vol. 6, no. 12, pp. 1455-1459, 2007.
65. H. W. Khella, M. Bakhet, G. Allo et al., "miR-192, miR-194 and miR-215: a convergent microRNA network suppressing tumor progression in renal cell carcinoma, " Carcinogenesis, vol. 34, no. 10, pp. 2231-2239, 2013.
66. C. J. Braun, X. Zhang, I. Savelyeva et al., "p53-responsive microRNAs 192 and 215 are capable of inducing cell cycle arrest, " Cancer Research, vol. 68, no. 24, pp. 10094-10104, 2008.
67. S. Feng, S. Cong, X. Zhang et al., "MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells, " Nucleic Acids Research, vol. 39, no. 15, pp. 6669-6678, 2011.
68. F. Pichiorri, S.-S. Suh, A. Rocci et al., "Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop inmultiplemyeloma development, " Cancer Cell, vol. 18, no. 4, pp. 367-381, 2010.
69. U. Senanayake, S. Das, P. Vesely et al., "miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms, " Carcinogenesis, vol. 33, no. 5, pp. 1014-1021, 2012.
70. S. A. Georges, M. C. Biery, S.-Y. Kim et al., "Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR-192 and miR-215, " Cancer Research, vol. 68, no. 24, pp. 10105-10112, 2008.
71. K. Polyak and R. A. Weinberg, "Transitions between epithelial andmesenchymal states: acquisition of malignant and stem cell traits, " Nature Reviews Cancer, vol. 9, no. 4, pp. 265-273, 2009.
72. S. Valastyan and R. A. Weinberg, "Tumormetastasis: molecular insights and evolving paradigms, " Cell, vol. 147, no. 2, pp. 275-292, 2011.
73. C. Chang, C. H. Chao, W. Xia et al., "P53 regulates epithelialmesenchymal transition and stem cell properties throughmodulating miRNAs, " Nature Cell Biology, vol. 13, no. 3, pp. 317-323, 2011.
74. T. Kim, A. Veronese, F. Pichiorri et al., "p53 regulates epithelialmesenchymal transition through microRNAs targeting ZEB1 and ZEB2, " Journal of Experimental Medicine, vol. 208, no. 5, pp. 875-883, 2011.
75. U. Burk, J. Schubert, U. Wellner et al., "A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells, " EMBO Reports, vol. 9, no. 6, pp. 582-589, 2008.
76. P. A. Gregory, A. G. Bert, E. L. Paterson et al., "The miR family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1, " Nature Cell Biology, vol. 10, no. 5, pp. 593-601, 2008.
77. M. Korpal, E. S. Lee, G. Hu, and Y. Kang, "The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2, "The Journal of Biological Chemistry, vol. 283, no. 22, pp. 14910-14914, 2008.
78. S.-M. Park, A. B. Gaur, E. Lengyel, and M. E. Peter, "ThemiR family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2, " Genes & Development, vol. 22, no. 7, pp. 894-907, 2008.
79. Y. Shimono, M. Zabala, R. W. Cho et al., "Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells, " Cell, vol. 138, no. 3, pp. 592-603, 2009.
80. U. Wellner, J. Schubert, U. C. Burk et al., "The EMT-activator ZEB1 promotes tumorigenicity by repressing stemnessinhibiting microRNAs, " Nature Cell Biology, vol. 11, no. 12, pp. 1487-1495, 2009.
81. R. Schickel, S.-M. Park, A. E. Murmann, and M. E. Peter, "miR-200c regulates induction of apoptosis through CD95 by targeting FAP-1, "Molecular Cell, vol. 38, no. 6, pp. 908-915, 2010.
82. A. E. Pasquinelli, B. J. Reinhart, F. Slack et al., "Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA, " Nature, vol. 408, no. 6808, pp. 86-89, 2000.
83. J. Takamizawa, H. Konishi, K. Yanagisawa et al., "Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival, " Cancer Research, vol. 64, no. 11, pp. 3753-3756, 2004.
84. N. Yanaihara, N. Caplen, E. Bowman et al., "Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, " Cancer Cell, vol. 9, no. 3, pp. 189-198, 2006.
85. A. D. Saleh, J. E. Savage, L. Cao et al., "Cellular stress induced alterations in microrna let-7a and let-7b expression are dependent on p53, " PLoS ONE, vol. 6, no. 10, Article ID e24429, 2011.
86. C. D. Johnson, A. Esquela-Kerscher, G. Stefani et al., "The let microRNA represses cell proliferation pathways in human cells, " Cancer Research, vol. 67, no. 16, pp. 7713-7722, 2007.
87. A. Legesse-Miller, O. Elemento, S. J. Pfau, J. J. Forman, S. Tavazoie, and H. A. Coller, "Let-7 overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of wee1 kinase in primary fibroblasts, " The Journal of Biological Chemistry, vol. 284, no. 11, pp. 6605-6609, 2009.
88. V. B. Sampson, N. H. Rong, J. Han et al., "MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells, " Cancer Research, vol. 67, no. 20, pp. 9762-9770, 2007.
89. M. J. Bueno, M. Gomez de Cedron, G. Gomez-Lopez et al., "Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway, " Blood, vol. 117, no. 23, pp. 6255-6266, 2011.
90. M. J. Bueno, M. G. de Cedron, U. Laresgoiti, J. Fernandez-Piqueras, A. M. Zubiaga, and M. Malumbres, "Multiple E2Finduced microRNAs prevent replicative stress in response to mitogenic signaling, "Molecular and Cellular Biology, vol. 30, no. 12, pp. 2983-2995, 2010.
91. A. Ota, H. Tagawa, S. Karnan et al., "Identification and characterization of a novel gene, C13orf25 , as a target for 13q31-q32 amplification in malignant lymphoma, " Cancer Research, vol. 64, no. 9, pp. 3087-3095, 2004.
92. L. He, J. M. Thomson, M. T. Hemann et al., "A microRNA polycistron as a potential human oncogene, " Nature, vol. 435, no. 7043, pp. 828-833, 2005.
93. H.-L. Yan, G. Xue, Q. Mei et al., "Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis, " EMBO Journal, vol. 28, no. 18, pp. 2719-2732, 2009.
94. K. A. ODonnell, E. A. Wentzel, K. I. Zeller, C. V. Dang, and J. T. Mendell, "c-Myc-regulated microRNAs modulate E2F1 expression, " Nature, vol. 435, no. 7043, pp. 839-843, 2005.
95. J. S. L. Ho, W. Ma, D. Y. L. Mao, and S. Benchimol, "p53-dependent transcriptional repression of c-myc is required for G1 cell cycle arrest, " Molecular and Cellular Biology, vol. 25, no. 17, pp. 7423-7431, 2005.
96. A. Hossain, M. T. Kuo, and G. F. Saunders, "Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA, "Molecular and Cellular Biology, vol. 26, no. 21, pp. 8191-8201, 2006.
97. H. Li and B. B. Yang, "Stress response of glioblastoma cells mediated by miR-17-5p targeting PTEN and the passenger strand miR-17-3p targeting MDM2, " Oncotarget, vol. 3, no. 12, pp. 1653-1668, 2012.
98. G. A. Calin, C. D. Dumitru, M. Shimizu et al., "Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia, " Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15524-15529, 2002.
99. A. Bottoni, D. Piccin, F. Tagliati, A. Luchin, M. C. Zatelli, and E. C. D. Uberti, "miR-15a and miR-16-1 down-regulation in pituitary adenomas, " Journal of Cellular Physiology, vol. 204, no. 1, pp. 280-285, 2005.
100. L. Xia, D. Zhang, R. Du et al., "miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells, " International Journal of Cancer, vol. 123, no. 2, pp. 372-379, 2008.
101. D. Bonci, V. Coppola, M. Musumeci et al., "The miR-15amiR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities, " Nature Medicine, vol. 14, no. 11, pp. 1271-1277, 2008.
102. F. Takeshita, L. Patrawala, M. Osaki et al., "Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes, " MolecularTherapy, vol. 18, no. 1, pp. 181-187, 2010.
103. M. Musumeci, V. Coppola, A. Addario et al., "Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer, " Oncogene, vol. 30, no. 41, pp. 4231-4242, 2011.
104. K. P. Porkka, E.-L. Ogg, O. R. Saramaki et al., "The miR-15amiR-16-1 locus is homozygously deleted in a subset of prostate cancers, " Genes, Chromosomes and Cancer, vol. 50, no. 7, pp. 499-509, 2011.
105. N. Bandi, S. Zbinden, M. Gugger et al., "miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer, " Cancer Research, vol. 69, no. 13, pp. 5553-5559, 2009.
106. N. Bandi and E. Vassella, "MiR-34a and miR-15a/16 are coregulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner, " Molecular Cancer, vol. 10, article 55, 2011.
107. R. Bhattacharya, M. Nicoloso, R. Arvizo et al., "MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer, " Cancer Research, vol. 69, no. 23, pp. 9090-9095, 2009.
108. X. J. Zhang, H. Ye, C. W. Zeng, B. He, H. Zhang, andY. Q. Chen, "Dysregulation of miR-15a and miR-214 in human pancreatic cancer, " Journal of Hematology & Oncology, vol. 3, article 46, 2010.
109. M. Fabbri, A. Bottoni, M. Shimizu et al., "Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia, " The Journal of the American Medical Association, vol. 305, no. 1, pp. 59-67, 2011.
110. H. I. Suzuki, K. Yamagata, K. Sugimoto, T. Iwamoto, S. Kato, and K. Miyazono, "Modulation of microRNA processing by p53, " Nature, vol. 460, no. 7254, pp. 529-533, 2009.
111. P. S. Linsley, J. Schelter, J. Burchard et al., "Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression, " Molecular and Cellular Biology, vol. 27, no. 6, pp. 2240-2252, 2007.
112. Q. Liu, H. Fu, F. Sun et al., "miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes, " Nucleic Acids Research, vol. 36, no. 16, pp. 5391-5404, 2008.
113. E. Macias, A. Jin, C. Deisenroth et al., "An ARF-Independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 interaction, " Cancer Cell, vol. 18, no. 3, pp. 231-243, 2010.
114. J. Zhang, Q. Sun, Z. Zhang, S. Ge, Z.-G. Han, and W.-T. Chen, "Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing theMDM2-p53 feedback loop, " Oncogene, vol. 32, no. 1, pp. 61-69, 2013.
115. J. Xiao, H. Lin, X. Luo, and Z. Wang, "miR605 joins p53 network to form a p53:miR605:Mdm2 positive feedback loop in response to stress, " EMBO Journal, vol. 30, no. 3, pp. 524-532, 2011.
116. S.-Y. Park, J. H. Lee, M. Ha, J.-W. Nam, and V. N. Kim, "miR miRNAs activate p53 by targeting p85α and CDC42, " Nature Structural and Molecular Biology, vol. 16, no. 1, pp. 23-29, 2009.
117. A. P. Ugalde, A. J. Ramsay, J. de la Rosa et al., "Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53, " EMBO Journal, vol. 30, no. 11, pp. 2219-2232, 2011.
118. K. Okamoto, H. Li, M. R. Jensen et al., "Cyclin G recruits PP2A to dephosphorylateMdm2, "Molecular Cell, vol. 9, no. 4, pp. 761-771, 2002.
119. F. Fornari, L. Gramantieri, C. Giovannini et al., "MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells, " Cancer Research, vol. 69, no. 14, pp. 5761-5767, 2009.
120. S.-S. Suh, J. Y. Yoo, G. J. Nuovo et al., "MicroRNAs/TP53 feedback circuitry in glioblastoma multiforme, " Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 14, pp. 5316-5321, 2012.
121. A. A. Dar, S. Majid, C. Rittsteuer et al., "The role of miR-18b in MDM2-p53 pathway signaling and melanoma progression, " Journal of the National Cancer Institute, vol. 105, no. 6, pp. 433-442, 2013.
122. J. Luo, A. Y. Nikolaev, S.-I. Imai et al., "Negative control of p53 by Sir2α promotes cell survival under stress, " Cell, vol. 107, no. 2, pp. 137-148, 2001.
123. H. Vaziri, S. K. Dessain, E. N. Eaton et al., "hSIR2 SIRT 1 functions as an NAD-dependent p53 deacetylase, " Cell, vol. 107, no. 2, pp. 149-159, 2001.
124. M. Yamakuchi, M. Ferlito, and C. J. Lowenstein, "miR-34a repression of SIRT1 regulates apoptosis, " Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 36, pp. 13421-13426, 2008.
125. M. Lize, S. Pilarski, and M. Dobbelstein, "E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis, " Cell Death & Differentiation, vol. 17, no. 3, pp. 452-458, 2010.
126. T. Bou Kheir, E. Futoma-Kazmierczak, A. Jacobsen et al., "miR inhibits cell proliferation and is down-regulated in gastric cancer, " Molecular Cancer, vol. 10, article 29, 2011.
127. M. Lize, A. Klimke, and M. Dobbelstein, "MicroRNA-449 in cell fate determination, " Cell Cycle, vol. 10, no. 17, pp. 2874-2882, 2011.
128. M. T. N. Le, C. Teh., N. Shyh-Chang et al., "MicroRNA-125b is a novel negative regulator of p53, " Genes and Development, vol. 23, no. 7, pp. 862-876, 2009.
129. Y. Zhang, J.-S. Gao, X. Tang et al., "MicroRNA 125a and its regulation of the p53 tumor suppressor gene, " FEBS Letters, vol. 583, no. 22, pp. 3725-3730, 2009.
130. N. Nishida, T. Yokobori, K. Mimori et al., "MicroRNA miR-125b is a prognostic marker in human colorectal cancer, " International Journal of Oncology, vol. 38, no. 5, pp. 1437-1443, 2011.
131. M. T. N. Le, N. Shyh-Chang, S. L. Khaw et al., "Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs, " PLoS Genetics, vol. 7, no. 9, Article IDe1002242, 2011.
132. W. Hu, C. S. Chan, R. Wu et al., "Negative regulation of tumor suppressor p53 by microRNA miR-504, "Molecular Cell, vol. 38, no. 5, pp. 689-699, 2010.
133. A. Swarbrick, S. L. Woods, A. Shawet al., "MiR-380-5p represses p53 to control cellular survival and is associated with poor outcome inMYCN-amplified neuroblastoma, " Nature Medicine, vol. 16, no. 10, pp. 1134-1140, 2010.
134. A. Herrera-Merchan, C. Cerrato, G. Luengo et al., "miR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewal, " Cell Cycle, vol. 9, no. 16, pp. 3277-3285, 2010.
135. S. Tian, S. Huang, S. Wu, W. Guo, J. Li, andX. He, "MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3′ untranslated region, " Biochemical and Biophysical Research Communications, vol. 396, no. 2, pp. 435-439, 2010.
136. J. Li, S. Donath, Y. Li, D. Qin, B. S. Prabhakar, and P. Li, "miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway, " PLoS Genetics, vol. 6, no. 1, Article ID e1000795, 2010.
137. M. Kumar, Z. Lu, A. A. L. Takwi et al., "Negative regulation of the tumor suppressor p53 gene by microRNAs, " Oncogene, vol. 30, no. 7, pp. 843-853, 2011.
138. N. Li, S. Kaur, J. Greshock et al., "A combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancer, " Cancer Research, vol. 72, no. 1, pp. 154-164, 2012.
139. L. Salmena, L. Poliseno, Y. Tay, L. Kats, and P. P. Pandolfi, "A ceRNA hypothesis: the rosetta stone of a hidden RNA language?" Cell, vol. 146, no. 3, pp. 353-358, 2011.
140. R. Schickel, B. Boyerinas, S.-M. Park, and M. E. Peter, "MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death, " Oncogene, vol. 27, no. 45, pp. 5959-5974, 2008.
141. N. Tsuchiya, M. Izumiya, H. Ogata-Kawata et al., "Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21, " Cancer Research, vol. 71, no. 13, pp. 4628-4639, 2011.
142. M. J. BuenoandM. Malumbres, "MicroRNAs andthe cell cycle, " Biochimica et Biophysica Acta, vol. 1812, no. 5, pp. 592-601, 2011.