Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1, ATF5, and EOMES in human hepatocellular carcinoma

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• 作者：Fei Gao (1)
  Yudong Xia (1)
  Junwen Wang (1)
  Zhilong Lin (1)
  Ying Ou (2) (3)
  Xing Liu (2) (3)
  Weilong Liu (4) (5)
  Boping Zhou (4) (5)
  Huijuan Luo (1)
  Baojin Zhou (1)
  Bo Wen (1)
  Xiuqing Zhang (1)
  Jian Huang (2) (3) (5)
  
• 刊名：Genome Biology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：12
• 全文大小：1,413 KB
• 参考文献：1. Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. / Lancet 2003, 362:1907鈥?917. CrossRef
  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. / Int J Cancer 2010, 127:2893鈥?917. CrossRef
  3. Sherman M: Recurrence of hepatocellular carcinoma. / N Engl J Med 2008, 359:2045鈥?047. CrossRef
  4. Nishida N, Goel A: Genetic and epigenetic signatures in human hepatocellular carcinoma: a systematic review. / Curr Genomics 2011, 12:130鈥?37. CrossRef
  5. Liu M, Jiang L, Guan XY: The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update. / Cell Protein 2014, 5:673鈥?91. CrossRef
  6. Anwar SL, Lehmann U: DNA methylation, microRNAs, and their crosstalk as potential biomarkers in hepatocellular carcinoma. / World J Gastroenterol 2014, 20:7894鈥?913. CrossRef
  7. Eden A, Gaudet F, Waghmare A, Jaenisch R: Chromosomal instability and tumors promoted by DNA hypomethylation. / Science 2003, 300:455. CrossRef
  8. Chan KC, Jiang P, Chan CW, Sun K, Wong J, Hui EP, Chan SL, Chan WC, Hui DS, Ng SS, Chan HLY, Wong CSC, Ma BBY, Chan ATC, Lai PBS, Sun H, Chiu RWK, Lo YMD: Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. / Proc Natl Acad Sci U S A 2013, 110:18761鈥?8768. CrossRef
  9. Nishida N, Kudo M, Nagasaka T, Ikai I, Goel A: Characteristic patterns of altered DNA methylation predict emergence of human hepatocellular carcinoma. / Hepatology 2012, 56:994鈥?003. CrossRef
  10. Umer M, Qureshi SA, Hashmi ZY, Raza A, Ahmad J, Rahman M, Iqbal M: Promoter hypermethylation of Wnt pathway inhibitors in hepatitis C virus - induced multistep hepatocarcinogenesis. / Virol J 2014, 11:117. CrossRef
  11. Shen J, Wang S, Zhang YJ, Wu HC, Kibriya MG, Jasmine F, Ahsan H, Wu DP, Siegel AB, Remotti H, Santella RM: Exploring genome-wide DNA methylation profiles altered in hepatocellular carcinoma using Infinium HumanMethylation 450 BeadChips. / Epigenetics 2013, 8:34鈥?3. CrossRef
  12. Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, Rao A: The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. / PLoS One 2010, 5:e8888. CrossRef
  13. Jin SG, Kadam S, Pfeifer GP: Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. / Nucleic Acids Res 2010, 38:e125. CrossRef
  14. Gao F, Xia Y: Hydroxymethylation- and methylation-sensitive tag sequencing: how will this technology change clinical applications of DNA methylation profiling? / Epigenomics 2013, 5:355鈥?57. CrossRef
  15. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A: Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. / Science 2009, 324:930鈥?35. CrossRef
  16. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y: Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. / Science 2011, 333:1300鈥?303. CrossRef
  17. Kriaucionis S, Heintz N: The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. / Science 2009, 324:929鈥?30. CrossRef
  18. Haffner MC, Chaux A, Meeker AK, Esopi DM, Gerber J, Pellakuru LG, Toubaji A, Argani P, Iacobuzio-Donahue C, Nelson WG, Netto GJ, De Marzo AM, Yegnasubramanian S: Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers. / Oncotarget 2011, 2:627鈥?37.
  19. Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, Xu ZD, Zhu HG, Ling ZQ, Ye D, Guan KL, Xiong Y: Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. / Oncogene 2013, 32:663鈥?69. CrossRef
  20. Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, Xu W, Tan L, Hu Y, Zhan Q, Lee CW, Hu D, Lian BQ, Kleffel S, Yang Y, Neiswender J, Khorasani AJ, Fang R, Lezcano C, Duncan LM, Scolyer RA, Thompson JF, Kavakand H, Houvras Y, Zon LI, Mihm MC Jr, Kaiser UB, Schatton T, Woda BA, Murphy GF, / et al: Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. / Cell 2012, 150:1135鈥?146. CrossRef
  21. Liu C, Liu L, Chen X, Shen J, Shan J, Xu Y, Yang Z, Wu L, Xia F, Bie P, Cui Y, Bian XW, Qian C: Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1. / PLoS One 2013, 8:e62828. CrossRef
  22. Gao F, Xia Y, Wang J, Luo H, Gao Z, Han X, Zhang J, Huang X, Yao Y, Lu H, Yi N, Zhou B, Lin Z, Wen B, Zhang X, Yang H, Wang J: Integrated detection of both 5-mC and 5-hmC by high-throughput tag sequencing technology highlights methylation reprogramming of bivalent genes during cellular differentiation. / Epigenetics 2013, 8:421鈥?30. CrossRef
  23. Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE: UHRF1 plays a role in maintaining DNA methylation in mammalian cells. / Science 2007, 317:1760鈥?764. CrossRef
  24. Bronner C, Krifa M, Mousli M: Increasing role of UHRF1 in the reading and inheritance of the epigenetic code as well as in tumorogenesis. / Biochem Pharmacol 2013, 86:1643鈥?649. CrossRef
  25. Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N, Zhu ZD, Zhou B, Liu XY, Liu RF, Fei QL, Chen H, Cai B, Zhou B, Xiao HS, Qin LX, Han ZG: Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. / Nat Genet 2012, 44:1117鈥?121. CrossRef
  26. Romer LH, Birukov KG, Garcia JG: Focal adhesions: paradigm for a signaling nexus. / Circ Res 2006, 98:606鈥?16. CrossRef
  27. Zhao J, Guan JL: Signal transduction by focal adhesion kinase in cancer. / Cancer Metastasis Rev 2009, 28:35鈥?9. CrossRef
  28. Fatima S, Lee NP, Luk JM: Dickkopfs and Wnt/beta-catenin signalling in liver cancer. / World J Clin Oncol 2011, 2:311鈥?25. CrossRef
  29. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC: The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. / Nature 2008, 452:230鈥?33. CrossRef
  30. Dong C, Yuan T, Wu Y, Wang Y, Fan TW, Miriyala S, Lin Y, Yao J, Shi J, Kang T, Lorkiewicz P, St Clair D, Hung MC, Evers BM, Zhou BP: Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. / Cancer Cell 2013, 23:316鈥?31. CrossRef
  31. Gao F, Zhang J, Jiang P, Gong D, Wang JW, Xia Y, Ostergaard MV, Wang J, Sangild PT: Marked methylation changes in intestinal genes during the perinatal period of preterm neonates. / BMC Genomics 2014, 15:716. CrossRef
  32. Neumann O, Kesselmeier M, Geffers R, Pellegrino R, Radlwimmer B, Hoffmann K, Ehemann V, Schemmer P, Schirmacher P, Lorenzo Bermejo J, Longerich T: Methylome analysis and integrative profiling of human HCCs identify novel protumorigenic factors. / Hepatology 2012, 56:1817鈥?827. CrossRef
  33. Heyn H, Esteller M: DNA methylation profiling in the clinic: applications and challenges. / Nat Rev Genet 2012, 13:679鈥?92. CrossRef
  34. Maunakea AK, Chepelev I, Cui K, Zhao K: Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. / Cell Res 2013, 23:1256鈥?269. CrossRef
  35. Hitchins MP, Rapkins RW, Kwok CT, Srivastava S, Wong JJ, Khachigian LM, Polly P, Goldblatt J, Ward RL: Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5'UTR. / Cancer Cell 2011, 20:200鈥?13. CrossRef
  36. Forn M, Munoz M, Tauriello DV, Merlos-Suarez A, Rodilla V, Bigas A, Batlle E, Jorda M, Peinado MA: Long range epigenetic silencing is a trans-species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells. / Mol Oncol 2013, 7:1129鈥?141. CrossRef
  37. Fujimoto N, Terlizzi J, Aho S, Brittingham R, Fertala A, Oyama N, McGrath JA, Uitto J: Extracellular matrix protein 1 inhibits the activity of matrix metalloproteinase 9 through high-affinity protein/protein interactions. / Exp Dermatol 2006, 15:300鈥?07. CrossRef
  38. Kessenbrock K, Plaks V, Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. / Cell 2010, 141:52鈥?7. CrossRef
  39. Pascual M, Gomez-Lechon MJ, Castell JV, Jover R: ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses. / Drug Metab Dispos 2008, 36:1063鈥?072. CrossRef
  40. Teske BF, Fusakio ME, Zhou D, Shan J, McClintick JN, Kilberg MS, Wek RC: CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis. / Mol Biol Cell 2013, 24:2477鈥?490. CrossRef
  41. Gho JW, Ip WK, Chan KY, Law PT, Lai PB, Wong N: Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest. / Cancer Res 2008, 68:6743鈥?751. CrossRef
  42. Liu X, Liu D, Qian D, Dai J, An Y, Jiang S, Stanley B, Yang J, Wang B, Liu DX: Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells. / J Biol Chem 2012, 287:19599鈥?9609. CrossRef
  43. Atreya I, Schimanski CC, Becker C, Wirtz S, Dornhoff H, Schnurer E, Berger MR, Galle PR, Herr W, Neurath MF: The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer. / Gut 2007, 56:1572鈥?578. CrossRef
  44. Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B: T-bet and eomesodermin are required for T cell-mediated antitumor immune responses. / J Immunol 2010, 185:3174鈥?183. CrossRef
  45. Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q: New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. / Br J Cancer 1999, 81:814鈥?21. CrossRef
  46. Li Y, Tang Z, Ye S, Liu Y, Chen J, Xue Q, Huang X, Bao W, Yang J, Gao D: [Establishment of human hepatocellular carcinoma cell line with spontaneous pulmonary metastasis through in vivo selection]. / Zhonghua Yi Xue Za Zhi 2002, 82:601鈥?05.
  47. Pelz CR, Kulesz-Martin M, Bagby G, Sears RC: Global rank-invariant set normalization (GRSN) to reduce systematic distortions in microarray data. / BMC Bioinformatics 2008, 9:520. CrossRef
  48. Zhang B, Kirov S, Snoddy J: WebGestalt: an integrated system for exploring gene sets in various biological contexts. / Nucleic Acids Res 2005, 33:W741鈥揥748. CrossRef
  49. Wang J, Duncan D, Shi Z, Zhang B: WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. / Nucleic Acids Res 2013, 41:W77鈥揥83. CrossRef
  50. WebGestalt. [http://www.webgestalt.org]
  51. St茅phane Audic J-MC: The significance of digital gene expression profiles. / Genome Res 1997, 7:986鈥?95.
  52. MethPrimer. [www.urogene.org/methprimer/index.html]
  
• 作者单位：Fei Gao (1)
  Yudong Xia (1)
  Junwen Wang (1)
  Zhilong Lin (1)
  Ying Ou (2) (3)
  Xing Liu (2) (3)
  Weilong Liu (4) (5)
  Boping Zhou (4) (5)
  Huijuan Luo (1)
  Baojin Zhou (1)
  Bo Wen (1)
  Xiuqing Zhang (1)
  Jian Huang (2) (3) (5)
  
  1. BGI-Shenzhen, Shenzhen, 518083, China
  2. National Engineering Center for Biochip at Shanghai, Shanghai, 201203, China
  3. Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, 201203, China
  4. Shenzhen Key Lab. of Infection and Immunity, Shenzhen Third People鈥檚 Hospital, Guangdong Medical College, Shenzhen, 518112, China
  5. Guangdong Key Lab. Of Diagnosis & Treatment for Emerging Infectious Disease, Shenzhen Third People鈥檚 Hospital, Guangdong Medical college, Shenzhen, 518112, China
  
• ISSN：1465-6906

文摘

Background Differences in 5-hydroxymethylcytosine, 5hmC, distributions may complicate previous observations of abnormal cytosine methylation statuses that are used for the identification of new tumor suppressor gene candidates that are relevant to human hepatocarcinogenesis. The simultaneous detection of 5-methylcytosine and 5-hydroxymethylcytosine is likely to stimulate the discovery of aberrantly methylated genes with increased accuracy in human hepatocellular carcinoma. Results Here, we performed ultra-performance liquid chromatography/tandem mass spectrometry and single-base high-throughput sequencing, Hydroxymethylation and Methylation Sensitive Tag sequencing, HMST-seq, to synchronously measure these two modifications in human hepatocellular carcinoma samples. After identification of differentially methylated and hydroxymethylated genes in human hepatocellular carcinoma, we integrate DNA copy-number alterations, as determined using array-based comparative genomic hybridization data, with gene expression to identify genes that are potentially silenced by promoter hypermethylation. Conclusions We report a high enrichment of genes with epigenetic aberrations in cancer signaling pathways. Six genes were selected as tumor suppressor gene candidates, among which, ECM1, ATF5 and EOMES are confirmed via siRNA experiments to have potential anti-cancer functions.