Phospho-ΔNp63α/microRNA network modulates epigenetic regulatory enzymes in squamous cell carcinomas

Cell Cycle

Volumn 13, Issue 5, 2014, Pages 749-761

  Ratovitski, Edward A ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Chemoresistance; DNA methylation; Epigenetic regulation; Histone deacetylation; Histone demethylation; microRNA; Squamous cell carcinomas; TP63

Indexed keywords

ANTINEOPLASTIC AGENT; BRM PROTEIN; CISPLATIN; DEATH ASSOCIATED PROTEIN KINASE; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; HISTONE DEACETYLASE; HISTONE DEACETYLASE 9; HISTONE DEACETYLASE INHIBITOR; IOX 1; MICRORNA; MICRORNA 101A; MICRORNA 148A; MICRORNA 181A; MICRORNA 22; MICRORNA 297; MICRORNA 29C; MICRORNA 34C; MICRORNA 374A; MICRORNA 429; MICRORNA 485; MICRORNA 519; MICRORNA 630; MICRORNA 885; MICRORNA 92B; MICRORNA 98; PROTEIN MDM2; PROTEIN P63; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; CKAP4 PROTEIN, HUMAN; DAPK1 PROTEIN, HUMAN; HISTONE DEMETHYLASE; MDM2 PROTEIN, HUMAN; MEMBRANE PROTEIN; PHOSPHOPROTEIN; SMARCA2 PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ARTICLE; CANCER RESISTANCE; CELL VIABILITY; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DNA METHYLATION; DOWN REGULATION; EPIGENETICS; GENE EXPRESSION; HISTONE METHYLATION; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SQUAMOUS CELL CARCINOMA; UPREGULATION; DRUG RESISTANCE; GENETIC EPIGENESIS; GENETICS; HUMAN; LARYNX TUMOR; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; CISPLATIN; DEATH-ASSOCIATED PROTEIN KINASES; DNA METHYLATION; DRUG RESISTANCE, NEOPLASM; EPIGENESIS, GENETIC; HISTONE DEACETYLASES; HISTONE DEMETHYLASES; HUMANS; LARYNGEAL NEOPLASMS; MEMBRANE PROTEINS; METABOLIC NETWORKS AND PATHWAYS; MICRORNAS; PHOSPHOPROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; TRANSCRIPTION FACTORS;

EID: 84897987602     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.27676     Document Type: Article

References (101)

1. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128:683-92; PMID:17320506; http://dx.doi.org/10.1016/j.cell.2007.01.029
2. Tsai HC, Baylin SB. Cancer epigenetics: linking basic biology to clinical medicine. Cell Res 2011; 21:502-17; PMID:21321605; http://dx.doi.org/10.1038/ cr.2011.24
3. Iorio MV, Piovan C, Croce CM. Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta 2010; 1799:694-701; PMID:20493980; http://dx.doi.org/10.1016/j.bbagrm.2010.05.005
4. Wiklund ED, Kjems J, Clark SJ. Epigenetic architecture and miRNA: reciprocal regulators. Epigenomics 2010; 2:823-40; PMID:22122085; http://dx.doi.org/10.2217/epi.10.51
5. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 12:861-74; PMID:22094949; http://dx.doi.org/10.1038/nrg3074
6. Lovat F, Valeri N, Croce CM. microRNAs in the pathogenesis of cancer. Semin Oncol 2011; 38:724-33; PMID:22082758; http://dx.doi.org/10.1053/j. seminoncol.2011.08.006
7. Pratt AJ, MacRae IJ. The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem 2009; 284:17897-901; PMID:19342379; http://dx.doi.org/10.1074/jbc.R900012200
8. van Kouwenhove M, Kedde M, Agami R. microRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer 2011; 11:644-56; PMID:21822212; http://dx.doi.org/10.1038/nrc3107
9. Sethupathy P, Megraw M, Hatzigeorgiou AG. A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods 2006; 3:881-6; PMID:17060911; http://dx.doi.org/10.1038/nmeth954
10. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006; 34:D140-4; PMID:16381832; http://dx.doi.org/10.1093/nar/gkj112
11. Pasquinelli AE. microRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 2012; 13:271-82; PMID:22411466
12. Calin GA, Croce CM. microRNA signatures in human cancers. Nat Rev Cancer 2006; 6:857-66; PMID:17060945; http://dx.doi.org/10.1038/nrc1997
13. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006; 103:2257-61; PMID:16461460; http://dx.doi.org/10.1073/pnas.0510565103
14. Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T, Hammond SM. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev 2006; 20:2202-7; PMID:16882971; http://dx.doi.org/10.1101/ gad.1444406
15. Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res 2007; 67:2456-68; PMID:17363563; http://dx.doi.org/10.1158/0008-5472.CAN-06-2698
16. Krutovskikh VA, Herceg Z. Oncogenic microRNAs (OncomiRs) as a new class of cancer biomarkers. Bioessays 2010; 32:894-904; PMID:21105295; http://dx.doi.org/10.1002/bies.201000040
17. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 2007; 39:673-7; PMID:17401365; http://dx.doi.org/10.1038/ng2003
18. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 2006; 9:435-43; PMID:16766263; http://dx.doi.org/10.1016/j.ccr.2006.04.020
19. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 2007; 26:745-52; PMID:17540599; http://dx.doi.org/10.1016/j.molcel.2007.05. 010
20. Gonzalez S, Pisano DG, Serrano M. Mechanistic principles of chromatin remodeling guided by siRNAs and miRNAs. Cell Cycle 2008; 7:2601-8; PMID:18719372; http://dx.doi.org/10.4161/cc.7.16.6541
21. Juan AH, Sartorelli V. microRNA-214 and polycomb group proteins: a regulatory circuit controlling differentiation and cell fate decisions. Cell Cycle 2010; 9:1445-6; PMID:20372071; http://dx.doi.org/10.4161/cc.9.8.11472
22. Kim T, Veronese A, Pichiorri F, Lee TJ, Jeon YJ, Volinia S, Pineau P, Marchio A, Palatini J, Suh SS, et al. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med 2011; 208:875-83; PMID:21518799; http://dx.doi.org/10.1084/jem.20110235
23. Kim DH, Saetrom P, Snøve O Jr., Rossi JJ. microRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A 2008; 105:16230-5; PMID:18852463; http://dx.doi.org/10.1073/pnas.0808830105
24. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. microRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 2008; 105:1608-13; PMID:18227514; http://dx.doi.org/10.1073/pnas.0707594105
25. Suzuki K, Kelleher AD. Transcriptional regulation by promoter targeted RNAs. Curr Top Med Chem 2009; 9:1079-87; PMID:19860708; http://dx.doi.org/10. 2174/156802609789630875
26. Younger ST, Corey DR. Transcriptional regulation by miRNA mimics that target sequences down-stream of gene termini. Mol Biosyst 2011; 7:2383-8; PMID:21589992; http://dx.doi.org/10.1039/c1mb05090g
27. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, et al. A microRNA component of the p53 tumour suppressor network. Nature 2007; 447:1130-4; PMID:17554337; http://dx.doi.org/10.1038/ nature05939
28. Huang Y, Kesselman D, Kizub D, Guerrero-Preston R, Ratovitski EA. Phospho-ΔNp63α/microRNA feedback regulation in squamous carcinoma cells upon cisplatin exposure. Cell Cycle 2013; 12:684-97; PMID:23343772; http://dx.doi.org/10.4161/cc.23598
29. Baer C, Claus R, Plass C. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 2013; 73:473-7; PMID:23316035; http://dx.doi.org/10.1158/ 0008-5472.CAN-12-3731
30. Iguchi H, Kosaka N, Ochiya T. Versatile applications of microRNA in anti-cancer drug discovery: from therapeutics to biomarkers. Curr Drug Discov Technol 2010; 7:95-105; PMID:20836759
31. Galasso M, Sana ME, Volinia S. Non-coding RNAs: a key to future personalized molecular therapy? Genome Med 2010; 2:12; PMID:20236487; http://dx.doi.org/10.1186/gm133
32. Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005; 438:685-9; PMID:16258535; http://dx.doi.org/10.1038/nature04303
33. Ebert MS, Neilson JR, Sharp PA. microRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4:721-6; PMID:17694064; http://dx.doi.org/10.1038/nmeth1079
34. Huang Y, Sen T, Nagpal J, Upadhyay S, Trink B, Ratovitski E, Sidransky D. ATM kinase is a master switch for the Δ Np63 α phosphorylation/ degradation in human head and neck squamous cell carcinoma cells upon DNA damage. Cell Cycle 2008; 7:2846-55; PMID:18769144; http://dx.doi.org/10.4161/cc. 7.18.6627
35. Huang Y, Chuang AY, Romano RA, Liégeois NJ, Sinha S, Trink B, Ratovitski E, Sidransky D. Phospho-DeltaNp63α/NF-Y protein complex transcriptionally regulates DDIT3 expression in squamous cell carcinoma cells upon cisplatin exposure. Cell Cycle 2010; 9:328-38; PMID:20023394; http://dx.doi.org/10.4161/cc.9.2.10432
36. Huang Y, Chuang A, Hao H, Talbot C, Sen T, Trink B, Sidransky D, Ratovitski E. Phospho-ΔNp63α is a key regulator of the cisplatin-induced microRNAome in cancer cells. Cell Death Differ 2011; 18:1220-30; PMID:21274007; http://dx.doi.org/10.1038/cdd.2010.188
37. Huang Y, Chuang AY, Ratovitski EA. Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure. Cell Cycle 2011; 10:3938-47; PMID:22071691; http://dx.doi.org/10.4161/cc.10.22.18107
38. Huang Y, Guerrero-Preston R, Ratovitski EA. Phospho-ΔNp63α- dependent regulation of autophagic signaling through transcription and microRNA modulation. Cell Cycle 2012; 11:1247-59; PMID:22356768; http://dx.doi.org/10. 4161/cc.11.6.19670
39. Ratovitski EA. Phospho-ΔNp63α-dependent microRNAs modulate chemoresistance of squamous cell carcinoma cells to cisplatin: at the crossroads of cell life and death. FEBS Lett 2013; 587:2536-41; PMID:23831023; http://dx.doi.org/10.1016/j.febslet.2013.06.020
40. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433:769-73; PMID:15685193; http://dx.doi.org/10.1038/nature03315
41. Bartel DP. microRNAs: target recognition and regulatory functions. Cell 2009; 136:215-33; PMID:19167326; http://dx.doi.org/10.1016/j.cell.2009.01.002
42. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010; 466:835-40; PMID:20703300; http://dx.doi.org/10.1038/nature09267
43. Huang Y, Jeong JS, Okamura J, Sook-Kim M, Zhu H, Guerrero-Preston R, Ratovitski EA. Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance. Cell Cycle 2012; 11:2367-79; PMID:22672905; http://dx.doi.org/10.4161/cc.20863
44. Huang Y, Ratovitski EA. Phospho-ΔNp63α/Rpn13-dependent regulation of LKB1 degradation modulates autophagy in cancer cells. Aging (Albany NY) 2010; 2:959-68; PMID:21191146
45. Hervouet E, Vallette FM, Cartron PF. Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. Epigenetics 2009; 4:487-99; PMID:19786833; http://dx.doi.org/10.4161/epi.4.7.9883
46. Hervouet E, Vallette FM, Cartron PF. Dnmt1/Transcription factor interactions: an alternative mechanism of DNA methylation inheritance. Genes Cancer 2010; 1:434-43; PMID:21779454; http://dx.doi.org/10.1177/1947601910373794
47. Ramsey MR, He L, Forster N, Ory B, Ellisen LW. Physical association of HDAC1 and HDAC2 with p63 mediates transcriptional repression and tumor maintenance in squamous cell carcinoma. Cancer Res 2011; 71:4373-9; PMID:21527555; http://dx.doi.org/10.1158/0008-5472.CAN-11-0046
48. Ho AS, Turcan S, Chan TA. Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management. Onco Targets Ther 2013; 6:223-32; PMID:23569385
49. Karaca B, Atmaca H, Bozkurt E, Kisim A, Uzunoglu S, Karabulut B, Sezgin C, Sanli UA, Uslu R. Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells. Mol Biol Rep 2013; 40:3925-33; PMID:23269627; http://dx.doi.org/10.1007/s11033- 012-2469-z
50. Sugita H, Iida S, Inokuchi M, Kato K, Ishiguro M, Ishikawa T, Takagi Y, Enjoji M, Yamada H, Uetake H, et al. Methylation of BNIP3 and DAPK indicates lower response to chemotherapy and poor prognosis in gastric cancer. Oncol Rep 2011; 25:513-8; PMID:21152877; http://dx.doi.org/10.3892/or.2010.1085
51. Ogawa T, Liggett TE, Melnikov AA, Monitto CL, Kusuke D, Shiga K, Kobayashi T, Horii A, Chatterjee A, Levenson VV, et al. Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance. Cell Cycle 2012; 11:1656-63; PMID:22487682; http://dx.doi.org/10. 4161/cc.20120
52. Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S. Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J 2002; 21:4183-95; PMID:12145218; http://dx.doi.org/ 10.1093/emboj/cdf401
53. Yokochi T, Robertson KD. Preferential methylation of unmethylated DNA by Mammalian de novo DNA methyltransferase Dnmt3a. J Biol Chem 2002; 277:11735-45; PMID:11821381; http://dx.doi.org/10.1074/jbc.M106590200
54. Oka M, Meacham AM, Hamazaki T, Rodić N, Chang LJ, Terada N. De novo DNA methyltransferases Dnmt3a and Dnmt3b primarily mediate the cytotoxic effect of 5-aza-2′-deoxycytidine. Oncogene 2005; 24:3091-9; PMID:15735669; http://dx.doi.org/10.1038/sj.onc.1208540
55. Jeong S, Liang G, Sharma S, Lin JC, Choi SH, Han H, Yoo CB, Egger G, Yang AS, Jones PA. Selective anchoring of DNA methyltransferases 3A and 3B to nucleosomes containing methylated DNA. Mol Cell Biol 2009; 29:5366-76; PMID:19620278; http://dx.doi.org/10.1128/MCB.00484-09
56. Jin B, Ernst J, Tiedemann RL, Xu H, Sureshchandra S, Kellis M, Dalton S, Liu C, Choi JH, Robertson KD. Linking DNA methyltransferases to epigenetic marks and nucleosome structure genome-wide in human tumor cells. Cell Rep 2012; 2:1411-24; PMID:23177624; http://dx.doi.org/10.1016/j.celrep.2012.10.017
57. Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD. Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res 2004; 32:598-610; PMID:14752048; http://dx.doi.org/10.1093/nar/gkh195
58. Joshi P, Greco TM, Guise AJ, Luo Y, Yu F, Nesvizhskii AI, Cristea IM. The functional interactome landscape of the human histone deacetylase family. Mol Syst Biol 2013; 9:672; PMID:23752268; http://dx.doi.org/10.1038/msb.2013.26
59. Clements EG, Mohammad HP, Leadem BR, Easwaran H, Cai Y, Van Neste L, Baylin SB. DNMT1 modulates gene expression without its catalytic activity partially through its interactions with histone-modifying enzymes. Nucleic Acids Res 2012; 40:4334-46; PMID:22278882; http://dx.doi.org/10.1093/nar/gks031
60. Bourachot B, Yaniv M, Muchardt C. Growth inhibition by the mammalian SWI-SNF subunit Brm is regulated by acetylation. EMBO J 2003; 22:6505-15; PMID:14657023; http://dx.doi.org/10.1093/emboj/cdg621
61. Glaros S, Cirrincione GM, Muchardt C, Kleer CG, Michael CW, Reisman D. The reversible epigenetic silencing of BRM: implications for clinical targeted therapy. Oncogene 2007; 26:7058-66; PMID:17546055; http://dx.doi.org/10.1038/sj. onc.1210514
62. Kahali B, Gramling SJ, Marquez SB, Thompson K, Lu L, Reisman D. Identifying targets for the restoration and reactivation of BRM. Oncogene 2014;33:653-64; PMID:23524580; http://dx.doi.org/10.1038/onc.2012.613.
63. Duong V, Bret C, Altucci L, Mai A, Duraffourd C, Loubersac J, Harmand PO, Bonnet S, Valente S, Maudelonde T, et al. Specific activity of class II histone deacetylases in human breast cancer cells. Mol Cancer Res 2008; 6:1908-19; PMID:19074835; http://dx.doi.org/10.1158/1541-7786.MCR-08-0299
64. Giannini G, Cabri W, Fattorusso C, Rodriquez M. Histone deacetylase inhibitors in the treatment of cancer: overview and perspectives. Future Med Chem 2012; 4:1439-60; PMID:22857533; http://dx.doi.org/10.4155/fmc.12.80
65. Cloos PA, Christensen J, Agger K, Helin K. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 2008; 22:1115-40; PMID:18451103; http://dx.doi.org/10.1101/gad.1652908
66. Pedersen MT, Helin K. Histone demethylases in development and disease. Trends Cell Biol 2010; 20:662-71; PMID:20863703; http://dx.doi.org/10.1016/j. tcb.2010.08.011
67. Varier RA, Timmers HT. Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta 2011; 1815:75-89; PMID:20951770
68. Luo W, Chang R, Zhong J, Pandey A, Semenza GL. Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Proc Natl Acad Sci U S A 2012; 109:E3367-76; PMID:23129632; http://dx.doi.org/10.1073/pnas.1217394109
69. Berry WL, Janknecht R. KDM4/JMJD2 histone demethylases: epigenetic regulators in cancer cells. Cancer Res 2013; 73:2936-42; PMID:23644528; http://dx.doi.org/10.1158/0008-5472.CAN-12-4300
70. Yang ZQ, Imoto I, Fukuda Y, Pimkhaokham A, Shimada Y, Imamura M, Sugano S, Nakamura Y, Inazawa J. Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines. Cancer Res 2000; 60:4735-9; PMID:10987278
71. Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T, Hansen KH, Helin K. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 2006; 442:307-11; PMID:16732293; http://dx.doi.org/10.1038/nature04837
72. Ishimura A, Terashima M, Kimura H, Akagi K, Suzuki Y, Sugano S, Suzuki T. Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene. Biochem Biophys Res Commun 2009; 389:366-71; PMID:19732750; http://dx.doi.org/10.1016/j. bbrc.2009.08.155
73. Suzuki T, Terashima M, Tange S, Ishimura A. Roles of histone methyl-modifying enzymes in development and progression of cancer. Cancer Sci 2013; 104:795-800; PMID:23560485; http://dx.doi.org/10.1111/cas.12169
74. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74; PMID:21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
75. Drakaki A, Iliopoulos D. microRNA Gene Networks in Oncogenesis. Curr Genomics 2009; 10:35-41; PMID:19721809; http://dx.doi.org/10.2174/ 138920209787581299
76. Sotiropoulou G, Pampalakis G, Lianidou E, Mourelatos Z. Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell. RNA 2009; 15:1443-61; PMID:19561119; http://dx.doi.org/10.1261/rna.1534709
77. Fabbri M, Calin GA. Epigenetics and miRNAs in human cancer. Adv Genet 2010; 70:87-99; PMID:20920746; http://dx.doi.org/10.1016/B978-0-12-380866-0. 60004-6
78. Ratovitski EA. Tumor Protein p63/microRNA network in epithelial cancer cells. Curr Genomics 2013; 14:441-52; http://dx.doi.org/10.2174/ 13892029113146660011
79. Lee TI, Young RA. Transcriptional regulation and its misregulation in disease. Cell 2013; 152:1237-51; PMID:23498934; http://dx.doi.org/10.1016/j. cell.2013.02.014
80. Shu XS, Li L, Tao Q. Chromatin regulators with tumor suppressor properties and their alterations in human cancers. Epigenomics 2012; 4:537-49; PMID:23130835; http://dx.doi.org/10.2217/epi.12.50
81. Kulaeva OI, Nizovtseva EV, Polikanov YS, Ulianov SV, Studitsky VM. Distant activation of transcription: mechanisms of enhancer action. Mol Cell Biol 2012; 32:4892-7; PMID:23045397; http://dx.doi.org/10.1128/MCB.01127-12
82. Zentner GE, Henikoff S. Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 2013; 20:259-66; PMID:23463310; http://dx.doi.org/10.1038/nsmb.2470
83. Sethupathy P. Illuminating microRNA Transcription from the Epigenome. Curr Genomics 2013; 14:68-77; PMID:23997652
84. Shalgi R, Brosh R, Oren M, Pilpel Y, Rotter V. Coupling transcriptional and post-transcriptional miRNA regulation in the control of cell fate. Aging (Albany NY) 2009; 1:762-70; PMID:20157565
85. Samantarrai D, Dash S, Chhetri B, Mallick B. Genomic and epigenomic cross-talks in the regulatory landscape of miRNAs in breast cancer. Mol Cancer Res 2013; 11:315-28; PMID:23360796; http://dx.doi.org/10.1158/1541-7786.MCR-12- 0649
86. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, et al. microRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 2007; 104:15805-10; PMID:17890317; http://dx.doi.org/10.1073/pnas.0707628104
87. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, et al. 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 2009; 113:6411-8; PMID:19211935; http://dx.doi.org/10.1182/blood-2008-07-170589
88. Benetti R, Gonzalo S, Jaco I, Muñoz P, Gonzalez S, Schoeftner S, Murchison E, Andl T, Chen T, Klatt P, et al. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol 2008; 15:268-79; PMID:18311151; http://dx.doi.org/10.1038/nsmb.1399
89. Duursma AM, Kedde M, Schrier M, le Sage C, Agami R. miR-148 targets human DNMT3b protein coding region. RNA 2008; 14:872-7; PMID:18367714; http://dx.doi.org/10.1261/rna.972008
90. Xu Q, Jiang Y, Yin Y, Li Q, He J, Jing Y, Qi YT, Xu Q, Li W, Lu B, et al. A regulatory circuit of miR-148a/152 and DNMT1 in modulating cell transformation and tumor angiogenesis through IGF-IR and IRS1. J Mol Cell Biol 2013; 5:3-13; PMID:22935141; http://dx.doi.org/10.1093/jmcb/mjs049
91. Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Hikiba Y, Obi S, Goto T, Kang YJ, Maeda S, Yoshida H, et al. microRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression. Hepatology 2013; 57:162-70; PMID:22898998; http://dx.doi.org/10.1002/hep.26011
92. Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K, et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 2008; 322:1695-9; PMID:19008416; http://dx.doi.org/10.1126/science.1165395
93. Zhang JG, Guo JF, Liu DL, Liu Q, Wang JJ. microRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. J Thorac Oncol 2011; 6:671-8; PMID:21270667; http://dx.doi.org/10.1097/JTO.0b013e318208eb35
94. Noonan EJ, Place RF, Pookot D, Basak S, Whitson JM, Hirata H, Giardina C, Dahiya R. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene 2009; 28:1714-24; PMID:19252524; http://dx.doi.org/10.1038/onc.2009.19
95. Buurman R, Gürlevik E, Schäffer V, Eilers M, Sandbothe M, Kreipe H, Wilkens L, Schlegelberger B, Kühnel F, Skawran B. Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells. Gastroenterology 2012; 143:811-20, e1-15; PMID:22641068; http://dx.doi.org/10.1053/j.gastro.2012.05.033
96. Yuan JH, Yang F, Chen BF, Lu Z, Huo XS, Zhou WP, Wang F, Sun SH. The histone deacetylase 4/SP1/microrna-200a regulatory network contributes to aberrant histone acetylation in hepatocellular carcinoma. Hepatology 2011; 54:2025-35; PMID:21837748; http://dx.doi.org/10.1002/hep.24606
97. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez- Céspedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A 2008; 105:13556-61; PMID:18768788; http://dx.doi.org/10.1073/ pnas.0803055105
98. Kutanzi KR, Yurchenko OV, Beland FA, Checkhun VF, Pogribny IP. microRNA-mediated drug resistance in breast cancer. Clin Epigenetics 2011; 2:171-85; PMID:21949547; http://dx.doi.org/10.1007/s13148-011-0040-8
99. Haenisch S, Cascorbi I. miRNAs as mediators of drug resistance. Epigenomics 2012; 4:369-81; PMID:22920178; http://dx.doi.org/10.2217/epi.12.39
100. DeYoung MP, Johannessen CM, Leong CO, Faquin W, Rocco JW, Ellisen LW. Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma. Cancer Res 2006; 66:9362-8; PMID:17018588; http://dx.doi.org/10.1158/ 0008-5472.CAN-06-1619
101. Rheinwald JG, Beckett MA. Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res 1981; 41:1657-63; PMID:7214336