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Regulation and Role of EZH2 in Cancer

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초록

Polycomb repressive complex 2 (PRC2) is the epigenetic regulator that induces histone H3lysine 27 methylation (H3K27me3) and silences specific gene transcription. Enhancer ofzeste homolog 2 (EZH2) is an enzymatic subunit of PRC2, and evidence shows that EZH2plays an essential role in cancer initiation, development, progression, metastasis, and drugresistance. EZH2 expression is indeed regulated by various oncogenic transcription factors,tumor suppressor miRNAs, and cancer-associated non-coding RNA. EZH2 activity is alsocontrolled by post-translational modifications, which are deregulated in cancer. The canonicalrole of EZH2 is gene silencing through H3K27me3, but accumulating evidence showsthat EZH2 methlyates substrates other than histone and has methylase-independentfunctions. These non-canonical functions of EZH2 are shown to play a role in cancerprogression. In this review, we summarize current information on the regulation and rolesof EZH2 in cancer. We also discuss various therapeutic approaches to targeting EZH2.

Abstract

Polycomb repressive complex 2 (PRC2) is the epigenetic regulator that induces histone H3lysine 27 methylation (H3K27me3) and silences specific gene transcription. Enhancer ofzeste homolog 2 (EZH2) is an enzymatic subunit of PRC2, and evidence shows that EZH2plays an essential role in cancer initiation, development, progression, metastasis, and drugresistance. EZH2 expression is indeed regulated by various oncogenic transcription factors,tumor suppressor miRNAs, and cancer-associated non-coding RNA. EZH2 activity is alsocontrolled by post-translational modifications, which are deregulated in cancer. The canonicalrole of EZH2 is gene silencing through H3K27me3, but accumulating evidence showsthat EZH2 methlyates substrates other than histone and has methylase-independentfunctions. These non-canonical functions of EZH2 are shown to play a role in cancerprogression. In this review, we summarize current information on the regulation and rolesof EZH2 in cancer. We also discuss various therapeutic approaches to targeting EZH2.

참고문헌 (174)

  1. Morey L, "Polycomb group protein-mediated repression of transcription", Trends Biochem Sci, 35, pp.323~332 (2010)
  2. Simon JA, "Mechanisms of polycomb gene silencing : knowns and unknowns", Nat Rev Mol Cell Biol, 10, pp.697~708 (2009)
  3. O'Meara MM, "Inner workings and regulatory inputs that control Polycomb repressive complex 2", Chromosoma, 121, pp.221~234 (2012)
  4. Koh CM, "Myc enforces overexpression of EZH2 in early prostatic neoplasia via transcriptional and post-transcriptional mechanisms", Oncotarget, 2, pp.669~683 (2011)
  5. Wang L, "c-Mycmediated epigenetic silencing of MicroRNA-101 contributes to dysregulation of multiple pathways in hepatocellular carcinoma", Hepatology, 59, pp.1850~1863 (2014)
  6. Sander S, "MYC stimulates EZH2 expression by repression of its negative regulator miR-26a", Blood, 112, pp.4202~4212 (2008)
  7. Salvatori B, "Critical role of c-Myc in acute myeloid leukemia involving direct regulation of miR-26a and histone methyltransferase EZH2", Genes Cancer, 2, pp.585~592 (2011)
  8. Suva ML, "EZH2 is essential for glioblastoma cancer stem cell maintenance", Cancer Res, 69, pp.9211~9218 (2009)
  9. Bracken AP, "EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer", EMBO J, 22, pp.5323~5335 (2003)
  10. Kalashnikova EV, "ANCCA", ATAD2 overexpression identifies breast cancer patients with poor prognosis, acting to drive proliferation and survival of triple-negative cells through control of B-Myb and EZH2, 2010, pp.70, 9402~9412
  11. Duan Z, "Developmental and androgenic regulation of chromatin regulators EZH2 and ANCCA", ATAD2 in the prostate via MLL histone methylase complex, 2013, pp.73, 455~466
  12. Richter GH, "EZH2 is a mediator of EWS", FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation, 2009, pp.106, 5324~5329
  13. Tiwari N, "Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming", Cancer Cell, 23, pp.768~783 (2013)
  14. Garipov A, "NF-YA underlies EZH2 upregulation and is essential for proliferation of human epithelial ovarian cancer cells", Mol Cancer Res, 11, pp.360~369 (2013)
  15. Lin YW, "Role of STAT3 and vitamin D receptor in EZH2-mediated invasion of human colorectal cancer", J Pathol, 230, pp.277~290 (2013)
  16. Kunderfranco P, "ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer", PLoS One, 5, pp.e10547~ (2010)
  17. Chang CJ, "EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-beta-catenin signaling", Cancer Cell, 19, pp.86~100 (2011)
  18. Fujii S, "MEKERK pathway regulates EZH2 overexpression in association with aggressive breast cancer subtypes", Oncogene, 30, pp.4118~4128 (2011)
  19. Esposito F, "Down-regulation of the miR-25 and miR- 30d contributes to the development of anaplastic thyroid carcinoma targeting the polycomb protein EZH2", J Clin Endocrinol Metab, 97, pp.E710~E718 (2012)
  20. Zhang B, "Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer", Carcinogenesis, 32, pp.2~9 (2011)
  21. Lu J, "MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2", Cancer Res, 71, pp.225~233 (2011)
  22. Varambally S, "Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer", Science, 322, pp.1695~1699 (2008)
  23. Friedman JM, "The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2", Cancer Res, 69, pp.2623~2629 (2009)
  24. Wang HJ, "MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion", Eur J Cancer, 46, pp.2295~2303 (2010)
  25. Banerjee R, "The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma", Oncogene, 30, pp.4339~4349 (2011)
  26. Smits M, "miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis", Oncotarget, 1, pp.710~720 (2010)
  27. Zhang JG, "MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2", J Thorac Oncol, 6, pp.671~678 (2011)
  28. Liu X, "MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines", Biochem J, 440, pp.23~31 (2011)
  29. Qiu S, "Suppression of tumorigenicity by microRNA-138 through inhibition of EZH2-CDK4", 6-pRb-E2F1 signal loop in glioblastoma multiforme, 2013, pp.1832, 1697~1707
  30. Zhang H, "MiR-138 inhibits tumor growth through repression of EZH2 in nonsmall cell lung cancer", Cell Physiol Biochem, 31, pp.56~65 (2013)
  31. Kong D, "Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM", PLoS One, 7, pp.e33729~ (2012)
  32. Cai K, "Let-7a inhibits proliferation and induces apoptosis by targeting EZH2 in nasopharyngeal carcinoma cells", Oncol Rep, 28, pp.2101~2106 (2012)
  33. Zheng F, "The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2", Gut, 61, pp.278~289 (2012)
  34. Xie L, "microRNA- 124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer", Mol Cell Biochem (2014)[DOI]
  35. Huang SD, "MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma", Mol Cancer, 11, pp.51~ (2012)
  36. Alajez NM, "Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98", Cell Death Dis, 1, pp.e85~ (2010)
  37. Luo C, "miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes", J Invest Dermatol, 133, pp.768~775 (2013)
  38. Guo Y, "miR-144 downregulation increases bladder cancer cell proliferation by targeting EZH2 and regulating Wnt signaling", FEBS J, 280, pp.4531~4538 (2013)
  39. Xia H, "MiR-214 targets beta-catenin pathway to suppress invasion, stem-like traits and recurrence of human hepatocellular carcinoma", PLoS One, 7, pp.e44206~ (2012)
  40. Shen J, "EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2", Nature, 497, pp.383~387 (2013)
  41. Caretti G, "The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation", Genes Dev, 18, pp.2627~2638 (2004)
  42. Yang Y, "A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma", Oncogene, 32, pp.3432~3442 (2013)
  43. Tong ZT, "EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1", HDAC2 and Snail to inhibit E-cadherin, 2012, pp.31, 583~594
  44. Corvetta D, "Physical interaction between MYCN oncogene and polycomb repressive complex 2(PRC2)in neuroblastoma : functional and therapeutic implications", J Biol Chem, 288, pp.8332~8341 (2013)
  45. Mukhopadhyay NK, "Scaffold attachment factor B1 regulates the androgen receptor in concert with the growth inhibitory kinase MST1 and the methyltransferase EZH2", Oncogene, 33, pp.3235~3245 (2014)
  46. Boulay G, "Hypermethylated in cancer 1(HIC1)recruits polycomb repressive complex 2(PRC2)to a subset of its target genes through interaction with human polycomb-like(hPCL)proteins", J Biol Chem, 287, pp.10509~10524 (2012)
  47. Hwang-Verslues WW, "Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy", Proc Natl Acad Sci U S A, 110, pp.12331~12336 (2013)
  48. Zhang H, "Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II", J Cell Biol, 193, pp.475~487 (2011)
  49. Leseva M, "E2f6-mediated repression of the meiotic Stag3 and Smc1beta genes during early embryonic development requires Ezh2 and not the de novo methyltransferase Dnmt3b", Epigenetics, 8, pp.873~884 (2013)
  50. Cakouros D, "Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A", Arf locus in mesenchymal stem cells, 2012, pp.32, 1433~1441
  51. Ciavatta DJ, "Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis", J Clin Invest, 120, pp.3209~3219 (2010)
  52. Gupta RA, "Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis", Nature, 464, pp.1071~1076 (2010)
  53. Kogo R, "Long noncoding RNA HOTAIR regulates polycombdependent chromatin modification and is associated with poor prognosis in colorectal cancers", Cancer Res, 71, pp.6320~6326 (2011)
  54. Kim K, "HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer", Oncogene, 32, pp.1616~1625 (2013)
  55. Liu Z, "The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1", CIP1) expression, 2013, pp.8, e77293~
  56. Tsai MC, "Long noncoding RNA as modular scaffold of histone modification complexes", Science, 329, pp.689~693 (2010)
  57. Yang F, "Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans", Hepatology, 54, pp.1679~1689 (2011)
  58. Prensner JR, "Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression", Nat Biotechnol, 29, pp.742~749 (2011)
  59. Luo M, "Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression", Cancer Lett, 333, pp.213~221 (2013)
  60. He W, "linc-UBC1 physically associates with polycomb repressive complex 2(PRC2)and acts as a negative prognostic factor for lymph node metastasis and survival in bladder cancer", Biochim Biophys Acta, 1832, pp.1528~1537 (2013)
  61. Zhao J, "Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome", Science, 322, pp.750~756 (2008)
  62. Rapicavoli NA, "The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity", Neural Dev, 6, pp.32~ (2011)
  63. Li Q, "AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans", Proc Natl Acad Sci U S A, 109, pp.14110~14115 (2012)
  64. Zhu L, "Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression", Biochem Biophys Res Commun, 432, pp.612~617 (2013)
  65. Kaneko S, "Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin", Mol Cell, 53, pp.290~300 (2014)
  66. Kim DH, "MicroRNA-directed transcriptional gene silencing in mammalian cells", Proc Natl Acad Sci U S A, 105, pp.16230~16235 (2008)
  67. Guil S, "Intronic RNAs mediate EZH2 regulation of epigenetic targets", Nat Struct Mol Biol, 19, pp.664~670 (2012)
  68. Wang L, "BRCA1 is a negative modulator of the PRC2 complex", EMBO J, 32, pp.1584~1597 (2013)
  69. Kaneko S, "Phosphorylation of the PRC2 component Ezh2 is cell cycleregulated and up-regulates its binding to ncRNA", Genes Dev, 24, pp.2615~2620 (2010)
  70. da Rocha ST, "Jarid2 is implicated in the initial Xist-induced targeting of PRC2 to the inactive X chromosome", Mol Cell, 53, pp.301~316 (2014)
  71. Cha TL, "Aktmediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3", Science, 310, pp.306~310 (2005)
  72. Xu K, "EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent", Science, 338, pp.1465~1469 (2012)
  73. Kim E, "Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells", Cancer Cell, 23, pp.839~852 (2013)
  74. Sahasrabuddhe AA, "Oncogenic Y641 mutations in EZH2 prevent Jak2", beta-TrCP-mediated degradation, 2014, ~
  75. Chen S, "Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2", Nat Cell Biol, 12, pp.1108~1114 (2010)
  76. Wu SC, "Cyclin-dependent kinase 1(CDK1)-mediated phosphorylation of enhancer of zeste 2(Ezh2)regulates its stability", J Biol Chem, 286, pp.28511~28519 (2011)
  77. Wei Y, "CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells", Nat Cell Biol, 13, pp.87~94 (2011)
  78. Minnebo N, "NIPP1 maintains EZH2 phosphorylation and promoter occupancy at proliferation-related target genes", Nucleic Acids Res, 41, pp.842~854 (2013)
  79. Li J, "EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia", Nat Neurosci, 16, pp.1745~1753 (2013)
  80. Palacios D, "TNF", p38alpha, Cell Stem Cell, pp.2010, 7[DOI]
  81. Chu CS, "O-GlcNAcylation regulates EZH2 protein stability and function", Proc Natl Acad Sci U S A, 111, pp.1355~1360 (2014)
  82. Riising EM, "The polycomb repressive complex 2 is a potential target of SUMO modifications", PLoS One, 3, pp.e2704~ (2008)
  83. Yu YL, "Smurf2-mediated degradation of EZH2 enhances neuron differentiation and improves functional recovery after ischaemic stroke", EMBO Mol Med, 5, pp.531~547 (2013)
  84. Zoabi M, "PRAJA1 is a ubiquitin ligase for the polycomb repressive complex 2 proteins", Biochem Biophys Res Commun, 408, pp.393~398 (2011)
  85. Lee J, "Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells", Cancer Cell, 13, pp.69~80 (2008)
  86. Morin RD, "Somatic mutations altering EZH2(Tyr641)in follicular and diffuse large B-cell lymphomas of germinal-center origin", Nat Genet, 42, pp.181~185 (2010)
  87. Sneeringer CJ, "Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3(H3K27)in human B-cell lymphomas", Proc Natl Acad Sci U S A, 107, pp.20980~20985 (2010)
  88. Beguelin W, "EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation", Cancer Cell, 23, pp.677~692 (2013)
  89. Majer CR, "A687V EZH2 is a gain-of-function mutation found in lymphoma patients", FEBS Lett, 586, pp.3448~3451 (2012)
  90. McCabe MT, "Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27(H3K27)", Proc Natl Acad Sci U S A, 109, pp.2989~2994 (2012)
  91. Lewis PW, "Inhibition of PRC2 activity by a gain-offunction H3 mutation found in pediatric glioblastoma", Science, 340, pp.857~861 (2013)
  92. Bender S, "Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas", Cancer Cell, 24, pp.660~672 (2013)
  93. Chan KM, "The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression", Genes Dev, 27, pp.985~990 (2013)
  94. Bachmann IM, "EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast", J Clin Oncol, 24, pp.268~273 (2006)
  95. Raman JD, "Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder", Clin Cancer Res, 11(24 Pt 1), pp.8570~8576 (2005)
  96. Matsukawa Y, "Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer", Cancer Sci, 97, pp.484~491 (2006)
  97. Kondo Y, "Alterations of DNA methylation and histone modifications contribute to gene silencing in hepatocellular carcinomas", Hepatol Res, 37, pp.974~983 (2007)
  98. Ougolkov AV, "Regulation of pancreatic tumor cell proliferation and chemoresistance by the histone methyltransferase enhancer of zeste homologue 2", Clin Cancer Res, 14, pp.6790~6796 (2008)
  99. Lee HW, "Expression of EZH2 in renal cell carcinoma as a novel prognostic marker", Pathol Int, 62, pp.735~741 (2012)
  100. Rao ZY, "EZH2 supports ovarian carcinoma cell invasion and", or metastasis via regulation of TGF-beta1 and is a predictor of outcome in ovarian carcinoma patients, 2010, pp.31, 1576~1583
  101. Crea F, "Clinical significance of Polycomb gene expression in brain tumors", Mol Cancer, 9, pp.265~ (2010)
  102. Yamada A, "Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus", Int J Oncol, 38, pp.345~353 (2011)
  103. Behrens C, "EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma", Clin Cancer Res, 19, pp.6556~6565 (2013)
  104. Alford SH, "Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression", Breast Cancer Res Treat, 132, pp.429~437 (2012)
  105. Crea F, "Pharmacologic disruption of Polycomb repressive complex 2 inhibits tumorigenicity and tumor progression in prostate cancer", Mol Cancer, 10, pp.40~ (2011)
  106. Gonzalez ME, "EZH2 expands breast stem cells through activation of NOTCH1 signaling", Proc Natl Acad Sci U S A, 111, pp.3098~3103 (2014)
  107. Li X, "Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia", Am J Pathol, 175, pp.1246~1254 (2009)
  108. Nikoloski G, "Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes", Nat Genet, 42, pp.665~667 (2010)
  109. Ernst T, "Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders", Nat Genet, 42, pp.722~726 (2010)
  110. Muto T, "Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders", J Exp Med, 210, pp.2627~2639 (2013)
  111. Ntziachristos P, "Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia", Nat Med, 18, pp.298~301 (2012)
  112. Simon C, "A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia", Genes Dev, 26, pp.651~656 (2012)
  113. Mallen-St Clair J, "EZH2 couples pancreatic regeneration to neoplastic progression", Genes Dev, 26, pp.439~444 (2012)
  114. Bracken AP, "The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells", Genes Dev, 21, pp.525~530 (2007)
  115. Ezhkova E, "Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells", Cell, 136, pp.1122~1135 (2009)
  116. Reynolds PA, "Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells", J Biol Chem, 281, pp.24790~24802 (2006)
  117. Sasaki M, "Over-expression of polycomb group protein EZH2 relates to decreased expression of p16 INK4a in cholangiocarcinogenesis in hepatolithiasis", J Pathol, 215, pp.175~183 (2008)
  118. Wang C, "Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma", Mol Carcinog, 52, pp.229~236 (2013)
  119. Yu H, "PRC2", EED-EZH2 complex is up-regulated in breast cancer lymph node metastasis compared to primary tumor and correlates with tumor proliferation in situ, 2012, pp.7, e51239~
  120. Fujii S, "Enhancer of zeste homolog 2 downregulates E-cadherin by mediating histone H3 methylation in gastric cancer cells", Cancer Sci, 99, pp.738~746 (2008)
  121. Cao Q, "Repression of E-cadherin by the polycomb group protein EZH2 in cancer", Oncogene, 27, pp.7274~7284 (2008)
  122. Chen Y, "Lentivirus-mediated RNA interference targeting enhancer of zeste homolog 2 inhibits hepatocellular carcinoma growth through down-regulation of stathmin", Hepatology, 46, pp.200~208 (2007)
  123. Cheng AS, "EZH2-mediated concordant repression of Wnt antagonists promotes beta-catenin-dependent hepatocarcinogenesis", Cancer Res, 71, pp.4028~4039 (2011)
  124. Yang X, "CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells", PLoS One, 4, pp.e5011~ (2009)
  125. Guo J, "EZH2 regulates expression of p57 and contributes to progression of ovarian cancer in vitro and in vivo", Cancer Sci, 102, pp.530~539 (2011)
  126. Yu J, "The neuronal repellent SLIT2 is a target for repression by EZH2 in prostate cancer", Oncogene, 29, pp.5370~5380 (2010)
  127. Wu L, "CCN3", NOV gene expression in human prostate cancer is directly suppressed by the androgen receptor, 2014, pp.33, 504~513
  128. Shin YJ, "The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cells", PLoS One, 7, pp.e30393~ (2012)
  129. Min J, "An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB", Nat Med, 16, pp.286~294 (2010)
  130. Du J, "FOXC1, a target of polycomb, inhibits metastasis of breast cancer cells", Breast Cancer Res Treat, 131, pp.65~73 (2012)
  131. Pathiraja TN, "Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer", Sci Transl Med, 6, pp.229~241 (2014)
  132. Zeidler M, "The Polycomb group protein EZH2 impairs DNA repair in breast epithelial cells", Neoplasia, 7, pp.1011~1019 (2005)
  133. Lu H, "Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC finger protein 4", Cell Death Dis, 4, pp.e776~ (2013)
  134. Marchesi I, "The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation", Cell Cycle, 11, pp.3828~3836 (2012)
  135. Wang C, "EZH2 mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR", Cancer Res, 72, pp.315~324 (2012)
  136. Fujii S, "Enhancer of zeste homologue 2(EZH2)down-regulates RUNX3 by increasing histone H3 methylation", J Biol Chem, 283, pp.17324~17332 (2008)
  137. Taniguchi H, "Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer", Oncogene, 31, pp.1988~1994 (2012)
  138. Wu ZL, "Polycomb protein EZH2 regulates E2F1-dependent apoptosis through epigenetically modulating Bim expression", Cell Death Differ, 17, pp.801~810 (2010)
  139. Tan J, "Phar-macologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells", Genes Dev, 21, pp.1050~1063 (2007)
  140. De Carvalho DD, "BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients", Oncogene, 30, pp.223~233 (2011)
  141. Lu C, "Regulation of tumor angiogenesis by EZH2", Cancer Cell, 18, pp.185~197 (2010)
  142. Asangani IA, "Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer", Mol Cell, 49, pp.80~93 (2013)
  143. Cao Q, "Coordinated regulation of Polycomb group complexes through microRNAs in cancer", Cancer Cell, 20, pp.187~199 (2011)
  144. Shi B, "Integration of estrogen and Wnt signaling circuits by the Polycomb group protein EZH2 in breast cancer cells", Mol Cell Biol, 27, pp.5105~5119 (2007)
  145. Jung HY, "PAF and EZH2 induce Wnt", beta-catenin signaling hyperactivation, 2013, pp.52, 193~205
  146. Lee ST, "Context- specific regulation of NF-kappaB target gene expression by EZH2 in breast cancers", Mol Cell, 43, pp.798~810 (2011)
  147. Yan J, "EZH2 overexpression in natural killer", T-cell lymphoma confers growth advantage independently of histone methyltransferase activity, 2013, pp.121, 4512~4520
  148. Lee JM, "EZH2 generates a methyl degron that is recognized by the DCAF1", DDB1, Mol Cell, pp.2012, 48[DOI]
  149. He A, "PRC2 directly methylates GATA4 and represses its transcriptional activity", Genes Dev, 26, pp.37~42 (2012)
  150. Su IH, "Polycomb group protein ezh2 controls actin polymerization and cell signaling", Cell, 121, pp.425~436 (2005)
  151. Bryant RJ, "The Polycomb group protein EZH2 regulates actin polymerization in human prostate cancer cells", Prostate, 68, pp.255~263 (2008)
  152. Campbell S, "Polycomb repressive complex 2 contributes to DNA doublestrand break repair", Cell Cycle, 12, pp.2675~2683 (2013)
  153. Gonzalez ME, "Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1", Oncogene, 28, pp.843~853 (2009)
  154. Gonzalez ME, "Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer", Cancer Res, 71, pp.2360~2370 (2011)
  155. Puppe J, "BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb repressive complex 2-inhibitor 3-deazaneplanocin A", Breast Cancer Res, 11, pp.R63~ (2009)
  156. Alimova I, "Targeting the enhancer of zeste homologue 2 in medulloblastoma", Int J Cancer, 131, pp.1800~1809 (2012)
  157. Kemp CD, "Polycomb repressor complex-2 is a novel target for mesothelioma therapy", Clin Cancer Res, 18, pp.77~90 (2012)
  158. Kalushkova A, "Polycomb target genes are silenced in multiple myeloma", PLoS One, 5, pp.e11483~ (2010)
  159. Gannon OM, "Dysregulation of the repressive H3K27 trimethylation mark in head and neck squamous cell carcinoma contributes to dysregulated squamous differentiation", Clin Cancer Res, 19, pp.428~441 (2013)
  160. Fujiwara T, "3-Deazaneplanocin A(DZNep), an inhibitor of S-adenosylmethionine-dependent methyltransferase, promotes erythroid differentiation", J Biol Chem, 289, pp.8121~8134 (2014)
  161. McCabe MT, "EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations", Nature, 492, pp.108~112 (2012)
  162. Knutson SK, "A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells", Nat Chem Biol, 8, pp.890~896 (2012)
  163. Knutson SK, "Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma", Mol Cancer Ther, 13, pp.842~854 (2014)
  164. Qi W, "Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation", Proc Natl Acad Sci U S A, 109, pp.21360~21365 (2012)
  165. Hua WF, "Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells", Eur J Pharmacol, 637, pp.16~21 (2010)
  166. Bao B, "Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression", Cancer Res, 72, pp.335~345 (2012)
  167. Dimri M, "Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells", Carcinogenesis, 31, pp.489~495 (2010)
  168. Wang S, "Sorafenib suppresses growth and survival of hepatoma cells by accelerating degradation of enhancer of zeste homolog 2", Cancer Sci, 104, pp.750~759 (2013)
  169. Avan A, "Molecular mechanisms involved in the synergistic interaction of the EZH2 inhibitor 3-deazaneplanocin A with gemcitabine in pancreatic cancer cells", Mol Cancer Ther, 11, pp.1735~1746 (2012)
  170. Fiskus W, "Superior efficacy of a combined epigenetic therapy against human mantle cell lymphoma cells", Clin Cancer Res, 18, pp.6227~6238 (2012)
  171. Hayden A, "S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER2 inhibition", Breast Cancer Res Treat, 127, pp.109~119 (2011)
  172. Sun F, "Combinatorial pharmacologic approaches target EZH2-mediated gene repression in breast cancer cells", Mol Cancer Ther, 8, pp.3191~3202 (2009)
  173. Lv Y, "The expression and significance of the enhancer of zeste homolog 2 in lung adenocarcinoma", Oncol Rep, 28, pp.147~154 (2012)
  174. Hu S, "Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo", Cancer Biol Ther, 10, pp.788~795 (2010)

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