REFERENCES
1. Feng J, Polychronidis G, Heger U, Frongia G, Mehrabi A, Hoffmann K. Incidence trends and survival prediction of hepatoblastoma in children: a population-based study. Cancer Commun (Lond) 2019;39:62.
3. Calvisi DF, Solinas A. Hepatoblastoma: current knowledge and promises from preclinical studies. Transl Gastroenterol Hepatol 2020;5:42.
4. Cairo S, Armengol C, Maibach R, et al. A combined clinical and biological risk classification improves prediction of outcome in hepatoblastoma patients. Eur J Cancer 2020;141:30-9.
5. Aronson DC, Schnater JM, Staalman CR, et al. Predictive value of the pretreatment extent of disease system in hepatoblastoma: results from the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study. J Clin Oncol 2005;23:1245-52.
6. Meyers RL, Maibach R, Hiyama E, et al. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration. Lancet Oncol 2017;18:122-31.
7. Ranganathan S, Lopez-Terrada D, Alaggio R. Hepatoblastoma and pediatric hepatocellular carcinoma: an update. Pediatr Dev Pathol 2020;23:79-95.
8. Perilongo G, Maibach R, Shafford E, et al. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 2009;361:1662-70.
9. Freyer DR, Brock PR, Chang KW, et al. Prevention of cisplatin-induced ototoxicity in children and adolescents with cancer: a clinical practice guideline. Lancet Child Adolesc Health 2020;4:141-50.
10. Marin JJG, Cives-Losada C, Asensio M, Lozano E, Briz O, Macias RIR. Mechanisms of anticancer drug resistance in hepatoblastoma. Cancers (Basel) 2019;11:407.
11. Jia D, Dong R, Jing Y, et al. Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex. Hepatology 2014;60:1686-96.
12. Eichenmüller M, Trippel F, Kreuder M, et al. The genomic landscape of hepatoblastoma and their progenies with HCC-like features. J Hepatol 2014;61:1312-20.
13. Gröbner SN, Worst BC, Weischenfeldt J, et al. ICGC PedBrain-Seq Project. The landscape of genomic alterations across childhood cancers. Nature 2018;555:321-7.
14. Cairo S, Armengol C, De Reyniès A, et al. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 2008;14:471-84.
15. Taniguchi K, Roberts LR, Aderca IN, et al. Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene 2002;21:4863-71.
16. Sumazin P, Chen Y, Treviño LR, et al. Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups. Hepatology 2017;65:104-21.
17. Hirsch TZ, Pilet J, Morcrette G, et al. Integrated genomic analysis identifies driver genes and cisplatin-resistant progenitor phenotype in pediatric liver cancer. Cancer Discov ;2021:candisc.
18. Carrillo-Reixach J, Torrens L, Simon-Coma M, et al. Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications. J Hepatol 2020;73:328-41.
19. Aretz S, Koch A, Uhlhaas S, et al. Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations? Pediatr Blood Cancer 2006;47:811-8.
20. Yang A, Sisson R, Gupta A, Tiao G, Geller JI. Germline APC mutations in hepatoblastoma. Pediatr Blood Cancer 2018;65:e26892.
21. Zhang Y, Solinas A, Cairo S, Evert M, Chen X, Calvisi DF. Molecular mechanisms of hepatoblastoma. Semin Liver Dis 2021;41:28-41.
22. Shen G, Shen H, Zhang J, Yan Q, Liu H. DNA methylation in hepatoblastoma-a literature review. Ital J Pediatr 2020;46:113.
23. Claveria-Cabello A, Colyn L, Arechederra M, et al. Epigenetics in liver fibrosis: could HDACs be a therapeutic target? Cells 2020;9:2321.
24. Barcena-Varela M, Colyn L, Fernandez-Barrena MG. Epigenetic mechanisms in hepatic stellate cell activation during liver fibrosis and carcinogenesis. Int J Mol Sci 2019;20:2507.
25. Maschietto M, Rodrigues TC, Kashiwabara AY, et al. DNA methylation landscape of hepatoblastomas reveals arrest at early stages of liver differentiation and cancer-related alterations. Oncotarget 2017;8:97871-89.
26. Li X, Kogner P, Sandstedt B, Haas OA, Ekström TJ. Promoter-specific methylation and expression alterations of igf2 and h19 are involved in human hepatoblastoma. Int J Cancer 1998;75:176-80.
27. Hartmann W, Waha A, Koch A, et al. p57KIP2 is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57KIP2, IGF2, and H19. Am J Pathol 2000;157:1393-403.
28. Honda S, Arai Y, Haruta M, et al. Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma. Br J Cancer 2008;99:1891-9.
30. Goel S, DeCristo MJ, McAllister SS, Zhao JJ. CDK4/6 inhibition in cancer: beyond cell cycle arrest. Trends Cell Biol 2018;28:911-25.
31. Zang JJ, Xie F, Xu JF, et al. P16 gene hypermethylation and hepatocellular carcinoma: a systematic review and meta-analysis. World J Gastroenterol 2011;17:3043-8.
32. Sterlacci W, Tzankov A, Veits L, et al. A comprehensive analysis of p16 expression, gene status, and promoter hypermethylation in surgically resected non-small cell lung carcinomas. J Thorac Oncol 2011;6:1649-57.
34. Shim YH, Park HJ, Choi MS, et al. Hypermethylation of the p16 gene and lack of p16 expression in hepatoblastoma. Mod Pathol 2003;16:430-6.
35. Harada K, Toyooka S, Maitra A, et al. Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines. Oncogene 2002;21:4345-9.
36. Malpeli G, Innamorati G, Decimo I, et al. Methylation dynamics of RASSF1A and its impact on cancer. Cancers (Basel) 2019;11:959.
37. Hesson LB, Cooper WN, Latif F. The role of RASSF1A methylation in cancer. Dis Markers 2007;23:73-87.
38. Khokhlatchev A, Rabizadeh S, Xavier R, et al. Identification of a novel Ras-regulated proapoptotic pathway. Current Biology 2002;12:253-65.
39. Law J, Salla M, Zare A, et al. Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein. J Biol Chem 2015;290:24100-18.
40. Baksh S, Tommasi S, Fenton S, et al. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Mol Cell 2005;18:637-50.
41. Fenton SL, Dallol A, Agathanggelou A, et al. Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene. Cancer Res 2004;64:102-7.
42. Zhang YJ, Ahsan H, Chen Y, et al. High frequency of promoter hypermethylation of RASSF1A and p16 and its relationship to aflatoxin B1-DNA adduct levels in human hepatocellular carcinoma. Mol Carcinog 2002;35:85-92.
43. Wong IH, Chan J, Wong J, Tam PK. Ubiquitous aberrant RASSF1A promoter methylation in childhood neoplasia. Clin Cancer Res 2004;10:994-1002.
44. Villanueva A, Portela A, Sayols S, et al. HEPTROMIC Consortium. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma. Hepatology 2015;61:1945-56.
45. Wong N, Li L, Tsang K, Lai PB, To K, Johnson PJ. Frequent loss of chromosome 3p and hypermethylation of RASSF1A in cholangiocarcinoma. J Hepatol 2002;37:633-9.
46. Yang B, House MG, Guo M, Herman JG, Clark DP. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol 2005;18:412-20.
47. Chen YJ, Tang QB, Zou SQ. Inactivation of RASSF1A, the tumor suppressor gene at 3p21.3 in extrahepatic cholangiocarcinoma. World J Gastroenterol 2005;11:1333-8.
48. Sugawara W, Haruta M, Sasaki F, et al. Promoter hypermethylation of the RASSF1A gene predicts the poor outcome of patients with hepatoblastoma. Pediatr Blood Cancer 2007;49:240-9.
49. Honda S, Haruta M, Sugawara W, et al. The methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients. Int J Cancer 2008;123:1117-25.
50. Honda S, Miyagi H, Suzuki H, et al. RASSF1A methylation indicates a poor prognosis in hepatoblastoma patients. Pediatr Surg Int 2013;29:1147-52.
51. Yeo W, Wong N, Wong WL, Lai PB, Zhong S, Johnson PJ. High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma. Liver Int 2005;25:266-72.
52. Liu G, Liu B, Zheng S, Dong K, Dong R. Aberrant RASSF5 gene transcribed region hypermethylation in pediatric hepatoblastomas. Int J Clin Exp Pathol 2018;11:3612-7.
53. Sprynski AC, Hose D, Kassambara A, et al. Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation. Leukemia 2010;24:1940-50.
54. Enguita-Germán M, Fortes P. Targeting the insulin-like growth factor pathway in hepatocellular carcinoma. World J Hepatol 2014;6:716-37.
55. Abdel-Rahman O. Insulin-like growth factor pathway aberrations and gastric cancer; evaluation of prognostic significance and assessment of therapeutic potentials. Med Oncol 2015;32:431.
56. Dziadziuszko R, Camidge DR, Hirsch FR. The insulin-like growth factor pathway in lung cancer. J Thorac Oncol 2008;3:815-8.
57. Nitulescu GM, Van De Venter M, Nitulescu G, et al. The Akt pathway in oncology therapy and beyond (Review). Int J Oncol 2018;53:2319-31.
58. Gray SG, Eriksson T, Ekström C, et al. Altered expression of members of the IGF-axis in hepatoblastomas. Br J Cancer 2000;82:1561-7.
59. Rumbajan JM, Maeda T, Souzaki R, et al. Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma. BMC Cancer 2013;13:608.
61. Akmal SN, Yun K, Maclay J, Higami Y, Ikeda T. Insulin-like growth factor 2 and insulin-like growth factor binding protein 2 expression in hepatoblastoma. Human Pathology 1995;26:846-51.
62. Williams AC, Collard TJ, Perks CM, et al. Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells. Cancer Res 2000;60:22-7.
63. Buckbinder L, Talbott R, Velasco-Miguel S, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature 1995;377:646-9.
64. Hanafusa T, Shinji T, Shiraha H, et al. Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation. BMC Cancer 2005;5:9.
65. López-Terrada D, Cheung SW, Finegold MJ, Knowles BB. Hep G2 is a hepatoblastoma-derived cell line. Hum Pathol 2009;40:1512-5.
66. Hanafusa T, Yumoto Y, Nouso K, et al. Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma. Cancer Letters 2002;176:149-58.
67. Tomii K, Tsukuda K, Toyooka S, et al. Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. Int J Cancer 2007;120:566-73.
68. Regel I, Eichenmüller M, Joppien S, et al. IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors. Mol Cancer 2012;11:9.
69. Nagai H, Naka T, Terada Y, et al. Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas. J Hum Genet 2003;48:65-9.
71. Bagnyukova TV, Tryndyak VP, Muskhelishvili L, Ross SA, Beland FA, Pogribny IP. Epigenetic downregulation of the suppressor of cytokine signaling 1 (Socs1) gene is associated with the STAT3 activation and development of hepatocellular carcinoma induced by methyl-deficiency in rats. Cell Cycle 2008;7:3202-10.
72. Huang FJ, Steeg PS, Price JE, et al. Molecular basis for the critical role of suppressor of cytokine signaling-1 in melanoma brain metastasis. Cancer Res 2008;68:9634-42.
73. Zhang J, Li H, Yu JP, Wang SE, Ren XB. Role of SOCS1 in tumor progression and therapeutic application. Int J Cancer 2012;130:1971-80.
74. Raccurt M, Tam SP, Lau P, et al. Suppressor of cytokine signalling gene expression is elevated in breast carcinoma. Br J Cancer 2003;89:524-32.
75. Guenterberg KD, Lesinski GB, Mundy-Bosse BL, et al. Enhanced anti-tumor activity of interferon-alpha in SOCS1-deficient mice is mediated by CD4+ and CD8+ T cells. Cancer Immunol Immunother 2011;60:1281-8.
76. Zimmerer JM, Lesinski GB, Kondadasula SV, et al. IFN-alpha-induced signal transduction, gene expression, and antitumor activity of immune effector cells are negatively regulated by suppressor of cytokine signaling proteins. J Immunol 2007;178:4832-45.
77. Sakamoto LH, DE Camargo B, Cajaiba M, Soares FA, Vettore AL. MT1G hypermethylation: a potential prognostic marker for hepatoblastoma. Pediatr Res 2010;67:387-93.
78. Tomlinson GE, Kappler R. Genetics and epigenetics of hepatoblastoma. Pediatr Blood Cancer 2012;59:785-92.
79. Russell JO, Monga SP. Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology. Annu Rev Pathol 2018;13:351-78.
80. Gao L, Zhang Z, Zhang P, Yu M, Yang T. Role of canonical Hedgehog signaling pathway in liver. Int J Biol Sci 2018;14:1636-44.
81. Zheng X, Zeng W, Gai X, et al. Role of the Hedgehog pathway in hepatocellular carcinoma (review). Oncol Rep 2013;30:2020-6.
82. Wang LH, Choi YL, Hua XY, et al. Increased expression of sonic hedgehog and altered methylation of its promoter region in gastric cancer and its related lesions. Mod Pathol 2006;19:675-83.
83. Tada M, Kanai F, Tanaka Y, et al. Down-regulation of hedgehog-interacting protein through genetic and epigenetic alterations in human hepatocellular carcinoma. Clin Cancer Res 2008;14:3768-76.
84. Eichenmüller M, Gruner I, Hagl B, et al. Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatology 2009;49:482-90.
85. Xu X, Li J, Sun X, et al. Tumor suppressor NDRG2 inhibits glycolysis and glutaminolysis in colorectal cancer cells by repressing c-Myc expression. Oncotarget 2015;6:26161-76.
86. Kim YJ, Yoon SY, Kim JT, et al. NDRG2 expression decreases with tumor stages and regulates TCF/beta-catenin signaling in human colon carcinoma. Carcinogenesis 2009;30:598-605.
87. Lusis EA, Watson MA, Chicoine MR, et al. Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Res 2005;65:7121-6.
88. Gödeke J, Luxenburger E, Trippel F, et al. Low expression of N-myc downstream-regulated gene 2 (NDRG2) correlates with poor prognosis in hepatoblastoma. Hepatol Int 2016;10:370-6.
89. Baharudin R, Tieng FYF, Lee LH, Ab Mutalib NS. Epigenetics of SFRP1: the dual roles in human cancers. Cancers (Basel) 2020;12:445.
90. Zhao CH, Bu XM, Zhang N. Hypermethylation and aberrant expression of Wnt antagonist secreted frizzled-related protein 1 in gastric cancer. World J Gastroenterol 2007;13:2214-7.
91. Wang X, Wang H, Bu R, Fei X, Zhao C, Song Y. Methylation and aberrant expression of the Wnt antagonist secreted Frizzled-related protein 1 in bladder cancer. Oncol Lett 2012;4:334-8.
92. Taguchi YH, Iwadate M, Umeyama H. SFRP1 is a possible candidate for epigenetic therapy in non-small cell lung cancer. BMC Med Genomics 2016;9 Suppl 1:28.
93. Kim J, Kim S. In silico identification of SFRP1 as a hypermethylated gene in colorectal cancers. Genomics Inform 2014;12:171-80.
94. Shih YL, Shyu RY, Hsieh CB, et al. Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer 2006;107:579-90.
95. Regel I, Eichenmüller M, Mahajan UM, et al. Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations. J Cancer Res Clin Oncol 2020;146:1153-67.
96. Shih YL, Hsieh CB, Lai HC, et al. SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway. Int J Cancer 2007;121:1028-35.
97. Honda S, Minato M, Suzuki H, et al. Clinical prognostic value of DNA methylation in hepatoblastoma: four novel tumor suppressor candidates. Cancer Sci 2016;107:812-9.
98. Rivas MP, Aguiar TFM, Maschietto M, et al. Hepatoblastomas exhibit marked NNMT downregulation driven by promoter DNA hypermethylation. Tumour Biol 2020;42:1010428320977124.
99. Li S, Qiao L, Yang Z, He C. Prognostic value of nicotinamide N-methyltransferase expression in patients with solid tumors: a systematic review and meta-analysis. Front Physiol 2018;9:1407.
100. Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat Chem Biol 2013;9:300-6.
101. Fujiyoshi S, Honda S, Minato M, et al. Hypermethylation of CSF3R is a novel cisplatin resistance marker and predictor of response to postoperative chemotherapy in hepatoblastoma. Hepatol Res 2020;50:598-606.
102. Zynger DL, Gupta A, Luan C, Chou PM, Yang GY, Yang XJ. Expression of glypican 3 in hepatoblastoma: an immunohistochemical study of 65 cases. Hum Pathol 2008;39:224-30.
103. Nguyen LH, Robinton DA, Seligson MT, et al. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. Cancer Cell 2014;26:248-61.
104. Meng W, Bai B, Bai Z, et al. The immunosuppression role of alpha-fetoprotein in human hepatocellular carcinoma. Discov Med 2016;21:489-94.
105. Cui X, Liu B, Zheng S, Dong K, Dong R. Genome-wide analysis of DNA methylation in hepatoblastoma tissues. Oncol Lett 2016;12:1529-34.
106. Fuhrman-Luck RA, Stansfield SH, Stephens CR, Loessner D, Clements JA. Prostate cancer-associated kallikrein-related peptidase 4 activates matrix metalloproteinase-1 and thrombospondin-1. J Proteome Res 2016;15:2466-78.
107. Wang P, Magdolen V, Seidl C, et al. Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer. Br J Cancer 2018;119:1-9.
108. Kontos CK, Chantzis D, Papadopoulos IN, Scorilas A. Kallikrein-related peptidase 4 (KLK4) mRNA predicts short-term relapse in colorectal adenocarcinoma patients. Cancer Lett 2013;330:106-12.
109. Liu B, Cui X, Zheng S, Dong K, Dong R. Aberrant KLK4 gene promoter hypomethylation in pediatric hepatoblastomas. Oncol Lett 2017;13:1360-4.
110. Vita M, Henriksson M. The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 2006;16:318-30.
111. Kress TR, Sabò A, Amati B. MYC: connecting selective transcriptional control to global RNA production. Nat Rev Cancer 2015;15:593-607.
112. Eberherr C, Beck A, Vokuhl C, et al. Targeting excessive MYCN expression using MLN8237 and JQ1 impairs the growth of hepatoblastoma cells. Int J Oncol 2019;54:1853-63.
113. Barcena-Varela M, Paish H, Alvarez L, et al. Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis. Gut 2021;70:388-400.
114. Bárcena-Varela M, Caruso S, Llerena S, et al. Dual targeting of histone methyltransferase G9a and DNA-methyltransferase 1 for the treatment of experimental hepatocellular carcinoma. Hepatology 2019;69:587-603.
115. Ding WJ, Fang JY, Chen XY, Peng YS. The expression and clinical significance of DNA methyltransferase proteins in human gastric cancer. Dig Dis Sci 2008;53:2083-9.
116. Tzelepi V, Logotheti S, Efstathiou E, et al. Epigenetics and prostate cancer: defining the timing of DNA methyltransferase deregulation during prostate cancer progression. Pathology 2020;52:218-27.
117. Colyn L, Bárcena-Varela M, Álvarez-Sola G, et al. Dual targeting of G9a and DNA Methyltransferase-1 for the treatment of experimental cholangiocarcinoma. Hepatology 2021;73:2380-96.
118. Li A, Omura N, Hong SM, Goggins M. Pancreatic cancer DNMT1 expression and sensitivity to DNMT1 inhibitors. Cancer Biol Ther 2010;9:321-9.
119. Rivas MP, Aguiar TFM, Fernandes GR, et al. TET upregulation leads to 5-hydroxymethylation enrichment in hepatoblastoma. Front Genet 2019;10:553.
120. Huang Y, Rao A. Connections between TET proteins and aberrant DNA modification in cancer. Trends Genet 2014;30:464-74.
121. Lin G, Sun W, Yang Z, Guo J, Liu H, Liang J. Hypoxia induces the expression of TET enzymes in HepG2 cells. Oncol Lett 2017;14:6457-62.
122. Liu C, Liu L, Chen X, et al. Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1. PLoS One 2013;8:e62828.
123. Sidhu H, Capalash N. UHRF1: The key regulator of epigenetics and molecular target for cancer therapeutics. Tumour Biol 2017;39:1010428317692205.
124. Jin W, Chen L, Chen Y, et al. UHRF1 is associated with epigenetic silencing of BRCA1 in sporadic breast cancer. Breast Cancer Res Treat 2010;123:359-73.
125. Sabatino L, Fucci A, Pancione M, et al. UHRF1 coordinates peroxisome proliferator activated receptor gamma (PPARG) epigenetic silencing and mediates colorectal cancer progression. Oncogene 2012;31:5061-72.
126. Zhuo H, Tang J, Lin Z, et al. The aberrant expression of MEG3 regulated by UHRF1 predicts the prognosis of hepatocellular carcinoma. Mol Carcinog 2016;55:209-19.
127. Ying L, Lin J, Qiu F, et al. Epigenetic repression of regulator of G-protein signaling 2 by ubiquitin-like with PHD and ring-finger domain 1 promotes bladder cancer progression. FEBS J 2015;282:174-82.
128. Zhou L, Shang Y, Jin Z, et al. UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation. Cancer Biol Ther 2015;16:1241-51.
129. Beck A, Trippel F, Wagner A, et al. Overexpression of UHRF1 promotes silencing of tumor suppressor genes and predicts outcome in hepatoblastoma. Clin Epigenetics 2018;10:27.
131. Gray SG, Hartmann W, Eriksson T, et al. Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas. Int J Mol Med 2000;6:161-9.
132. Kuo P, Chiang L, Lin C. Resveratrol- induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life Sciences 2002;72:23-34.
133. West AC, Johnstone RW. New and emerging HDAC inhibitors for cancer treatment. J Clin Invest 2014;124:30-9.
134. Singh AK, Bishayee A, Pandey AK. Targeting histone deacetylases with natural and synthetic agents: an emerging anticancer strategy. Nutrients 2018;10:731.
135. Venturelli S, Berger A, Böcker A, et al. Resveratrol as a pan-HDAC inhibitor alters the acetylation status of histone [corrected] proteins in human-derived hepatoblastoma cells. PLoS One 2013;8:e73097.
136. Beck A, Eberherr C, Hagemann M, et al. Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma. Cancer Biol Ther 2016;17:1168-76.
137. French C. . Small-molecule targeting of BET proteins in cancer. Elsevier; 2016. p. 21-58.
138. Wang YH, Sui XM, Sui YN, et al. BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway. Oncol Lett 2015;10:2227-32.
139. Saltsman JA, Hammond WJ, Narayan NJC, et al. A human organoid model of aggressive hepatoblastoma for disease modeling and drug testing. Cancers (Basel) 2020;12:2668.
140. Chen Y, Ren B, Yang J, et al. The role of histone methylation in the development of digestive cancers: a potential direction for cancer management. Signal Transduct Target Ther 2020;5:143.
142. Wang Y, Xiao Y, Chen K, et al. Enhancer of zeste homolog 2 depletion arrests the proliferation of hepatoblastoma cells. Mol Med Rep 2016;13:2724-8.
143. Schlachter K, Gyugos M, Halász J, et al. High tricellulin expression is associated with better survival in human hepatoblastoma. Histopathology 2014;65:631-41.
144. Wong LS, Wong CM. Decoding the roles of long noncoding RNAs in hepatocellular carcinoma. Int J Mol Sci 2021;22:3137.
145. Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci 2020;21:1723.
146. Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. a comprehensive review. EMBO Mol Med 2012;4:143-59.
147. Magrelli A, Azzalin G, Salvatore M, et al. Altered microRNA expression patterns in hepatoblastoma patients. Transl Oncol 2009;2:157-63.
148. Gyugos M, Lendvai G, Kenessey I, et al. MicroRNA expression might predict prognosis of epithelial hepatoblastoma. Virchows Arch 2014;464:419-27.
149. Ecevit ÇÖ, Aktaş S, Tosun Yildirim H, et al. MicroRNA-17, microRNA-19b, microRNA-146a, microRNA-302d expressions in hepatoblastoma and clinical importance. J Pediatr Hematol Oncol 2019;41:7-12.
150. Zatkova A, Rouillard JM, Hartmann W, et al. Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. Genes Chromosomes Cancer 2004;39:126-37.
151. Voz ML, Mathys J, Hensen K, et al. Microarray screening for target genes of the proto-oncogene PLAG1. Oncogene 2004;23:179-91.
152. Frowein J, Pagel P, Kappler R, von Schweinitz D, Roscher A, Schmid I. MicroRNA-492 is processed from the keratin 19 gene and up-regulated in metastatic hepatoblastoma. Hepatology 2011;53:833-42.
153. von Frowein J, Hauck SM, Kappler R, et al. MiR-492 regulates metastatic properties of hepatoblastoma via CD44. Liver Int 2018;38:1280-91.
154. Yin DT, Wu W, Li M, et al. DKK3 is a potential tumor suppressor gene in papillary thyroid carcinoma. Endocr Relat Cancer 2013;20:507-14.
155. Veeck J, Wild PJ, Fuchs T, et al. Prognostic relevance of Wnt-inhibitory factor-1 (WIF1) and Dickkopf-3 (DKK3) promoter methylation in human breast cancer. BMC Cancer 2009;9:217.
156. Li Q, Shen K, Zhao Y, Ma C, Liu J, Ma J. MiR-92b inhibitor promoted glioma cell apoptosis via targeting DKK3 and blocking the Wnt/beta-catenin signaling pathway. J Transl Med 2013;11:302.
157. Farkas SA, Vymetalkova V, Vodickova L, Vodicka P, Nilsson TK. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes. Epigenomics 2014;6:179-91.
158. Pei Y, Kano J, Iijima T, Morishita Y, Inadome Y, Noguchi M. Overexpression of Dickkopf 3 in hepatoblastomas and hepatocellular carcinomas. Virchows Arch 2009;454:639-46.
159. Pei Y, Yao Q, Yuan S, et al. GATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3. Oncotarget 2016;7:77890-901.
160. Cairo S, Wang Y, de Reyniès A, et al. Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Proc Natl Acad Sci U S A 2010;107:20471-6.
161. Weiss JBW, Wagner AE, Eberherr C, et al. High expression of IGF2-derived intronic miR-483 predicts outcome in hepatoblastoma. Cancer Biomark 2020;28:321-8.
162. Cartier F, Indersie E, Lesjean S, et al. New tumor suppressor microRNAs target glypican-3 in human liver cancer. Oncotarget 2017;8:41211-26.
163. Samuels-lev Y, O'connor DJ, Bergamaschi D, et al. ASPP proteins specifically stimulate the apoptotic function of p53. Molecular Cell 2001;8:781-94.
164. Liang B, Chen R, Song S, et al. ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma. Cell Death Dis 2019;10:830.
165. Liu L, Wang L, Li X, et al. Effect of miR-21 on apoptosis in hepatoblastoma cell through activating ASPP2/p38 signaling pathway in vitro and in vivo. Artif Cells Nanomed Biotechnol 2019;47:3729-36.
166. Honda S, Chatterjee A, Leichter AL, et al. A microRNA cluster in the DLK1-DIO3 imprinted region on chromosome 14q32.2 is dysregulated in metastatic hepatoblastomas. Front Oncol 2020;10:513601.
167. Chen LJ, Yuan MX, Ji CY, et al. Long non-coding RNA CRNDE regulates angiogenesis in hepatoblastoma by targeting the MiR-203/VEGFA axis. Pathobiology 2020;87:161-70.
168. Song H, Bian ZX, Li HY, et al. Characterization of hsa_circ_0000594 as a new biomarker and therapeutic target for hepatoblastoma. Eur Rev Med Pharmacol Sci 2019;23:8274-86.
169. Zhen N, Gu S, Ma J, et al. CircHMGCS1 promotes hepatoblastoma cell proliferation by regulating the IGF signaling pathway and glutaminolysis. Theranostics 2019;9:900-19.
170. Liu Y, Song J, Liu Y, Zhou Z, Wang X. Transcription activation of circ-STAT3 induced by Gli2 promotes the progression of hepatoblastoma via acting as a sponge for miR-29a/b/c-3p to upregulate STAT3/Gli2. J Exp Clin Cancer Res 2020;39:101.
171. Galardi A, Colletti M, Di Paolo V, et al. Exosomal miRNAs in pediatric cancers. Int J Mol Sci 2019;20:4600.
172. Jiao C, Jiao X, Zhu A, Ge J, Xu X. Exosomal miR-34s panel as potential novel diagnostic and prognostic biomarker in patients with hepatoblastoma. J Pediatr Surg 2017;52:618-24.
173. Nandwani A, Rathore S, Datta M. LncRNAs in cancer: regulatory and therapeutic implications. Cancer Lett 2021;501:162-71.
175. Dong R, Jia D, Xue P, et al. Genome-wide analysis of long noncoding RNA (lncRNA) expression in hepatoblastoma tissues. PLoS One 2014;9:e85599.
176. Wang XD, Peng JB, Zhou CY, et al. Potential therapies for residual hepatoblastoma following incomplete ablation treatment in a nude mouse subcutaneous xenograft model based on lncRNA and mRNA expression profiles. Oncol Rep 2020;43:1915-27.
177. Alipoor B, Parvar SN, Sabati Z, Ghaedi H, Ghasemi H. An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance. Mol Biol Rep 2020;47:6357-74.
178. Li J, Zhang M, An G, Ma Q. LncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis. Exp Biol Med (Maywood) 2016;241:644-9.
179. Zhang EB, Yin DD, Sun M, et al. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 2014;5:e1243.
180. Fan S, Yang Z, Ke Z, et al. Downregulation of the long non-coding RNA TUG1 is associated with cell proliferation, migration, and invasion in breast cancer. Biomed Pharmacother 2017;95:1636-43.
181. Ma B, Li M, Zhang L, et al. Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumour Biol 2016;37:4445-55.
182. Zhai HY, Sui MH, Yu X, et al. Overexpression of long non-coding RNA TUG1 promotes colon cancer progression. Med Sci Monit 2016;22:3281-7.
183. Huang MD, Chen WM, Qi FZ, et al. Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2. Mol Cancer 2015;14:165.
184. Dong R, Liu GB, Liu BH, et al. Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma. Cell Death Dis 2016;7:e2278.
185. Zhang J, Yin M, Peng G, Zhao Y. CRNDE: an important oncogenic long non-coding RNA in human cancers. Cell Prolif 2018;51:e12440.
186. Dong R, Liu XQ, Zhang BB, Liu BH, Zheng S, Dong KR. Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma. Oncotarget 2017;8:42087-97.
187. Lv B, Zhang L, Miao R, et al. Comprehensive analysis and experimental verification of LINC01314 as a tumor suppressor in hepatoblastoma. Biomed Pharmacother 2018;98:783-92.
188. Yu Q, Li Y, Peng S, Li J, Qin X. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p. Open Med (Wars) 2021;16:512-25.
189. Zhang Z, Liu F, Yang F, Liu Y. Kockdown of OIP5-AS1 expression inhibits proliferation, metastasis and EMT progress in hepatoblastoma cells through up-regulating miR-186a-5p and down-regulating ZEB1. Biomed Pharmacother 2018;101:14-23.
190. Li A, Feng L, Niu X, Zeng Q, Li B, You Z. Downregulation of OIP5-AS1 affects proNGF-induced pancreatic cancer metastasis by inhibiting p75NTR levels. Aging (Albany NY) 2021;13:10688-702.
191. Wang X, Guo S, Zhao R, Liu Y, Yang G. STAT3-activated long non-coding RNA lung cancer associated transcript 1 drives cell proliferation, migration, and invasion in hepatoblastoma through regulation of the miR-301b/STAT3 axis. Hum Gene Ther 2019;30:702-13.
192. Cui X, Wang Z, Liu L, et al. The long non-coding RNA ZFAS1 sponges miR-193a-3p to modulate hepatoblastoma growth by targeting RALY via HGF/c-Met pathway. Front Cell Dev Biol 2019;7:271.
193. Burenina OY, Lazarevich NL, Kustova IF, et al. Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors. J Cancer Res Clin Oncol 2021;147:49-59.
194. Jiao S, Wu S, Huang S, Liu M, Gao B. Advances in the identification of circular RNAs and research into circRNAs in human diseases. Front Genet 2021;12:665233.
195. Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013;495:384-8.
196. Yang Y, Fan X, Mao M, et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res 2017;27:626-41.
197. Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 2015;22:256-64.
198. Conn VM, Hugouvieux V, Nayak A, et al. A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation. Nat Plants 2017;3:17053.
199. Zhong Z, Lv M, Chen J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep 2016;6:30919.
200. Li P, Chen S, Chen H, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta 2015;444:132-6.
201. Tang Y, Jiang M, Jiang HM, et al. The roles of circRNAs in liver cancer immunity. Front Oncol 2020;10:598464.
202. Liu BH, Zhang BB, Liu XQ, Zheng S, Dong KR, Dong R. Expression profiling identifies circular RNA signature in hepatoblastoma. Cell Physiol Biochem 2018;45:706-19.
203. Lee H, Kim KR, Noh SJ, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma. Hum Pathol 2011;42:204-13.
204. Zhang ZY, Hong D, Nam SH, et al. SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma. J Hepatol 2015;62:121-30.
205. Matés JM, Campos-Sandoval JA, Santos-Jiménez JL, Márquez J. Dysregulation of glutaminase and glutamine synthetase in cancer. Cancer Lett 2019;467:29-39.
206. Chen L, Shi J, Wu Y, et al. CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression. Aging (Albany NY) 2020;12:19233-53.
207. Zhao BS, Roundtree IA, He C. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol 2017;18:31-42.
208. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012;485:201-6.
209. Wang X, Lu Z, Gomez A, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 2014;505:117-20.
210. Xu Y, Zhang W, Shen F, et al. YTH domain proteins: a family of m6A readers in cancer progression. Front Oncol 2021;11:629560.
211. Chen M, Wei L, Law CT, et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology 2018;67:2254-70.
212. Liu L, Wang J, Sun G, et al. m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma. Mol Cancer 2019;18:188.
213. Cui X, Wang Z, Li J, et al. Cross talk between RNA N6-methyladenosine methyltransferase-like 3 and miR-186 regulates hepatoblastoma progression through Wnt/β-catenin signalling pathway. Cell Prolif 2020;53:e12768.
214. Zhuo ZJ, Hua RX, Chen Z, et al. WTAP gene variants confer hepatoblastoma susceptibility: a seven-center case-control study. Mol Ther Oncolytics 2020;18:118-25.
215. Han L, Diao L, Yu S, et al. The genomic landscape and clinical relevance of A-to-I RNA editing in human cancers. Cancer Cell 2015;28:515-28.
216. Paz-Yaacov N, Bazak L, Buchumenski I, et al. Elevated RNA editing activity is a major contributor to transcriptomic diversity in tumors. Cell Rep 2015;13:267-76.
217. Galeano F, Leroy A, Rossetti C, et al. Human BLCAP transcript: new editing events in normal and cancerous tissues. Int J Cancer 2010;127:127-37.
218. Feng S, De Carvalho DD. Clinical advances in targeting epigenetics for cancer therapy. FEBS J 2021; doi: 10.1111/febs.15750.
219. El Sayed S, Cristante J, Guyon L, Denis J, Chabre O, Cherradi N. MicroRNA Therapeutics in cancer: current advances and challenges. Cancers (Basel) 2021;13:2680.
220. Oronsky B, Oronsky N, Knox S, Fanger G, Scicinski J. Episensitization: therapeutic tumor resensitization by epigenetic agents: a review and reassessment. Anticancer Agents Med Chem 2014;14:1121-7.
221. Oronsky BT, Oronsky AL, Lybeck M, et al. Episensitization: defying time's arrow. Front Oncol 2015;5:134.
222. Li GH, Qu Q, Qi TT, et al. Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance. J Exp Clin Cancer Res 2021;40:174.
223. Yang T, Yang Y, Wang Y. Predictive biomarkers and potential drug combinations of epi-drugs in cancer therapy. Clin Epigenetics 2021;13:113.
224. Wei QY, Xu YM, Lau ATY. Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies. Cancers (Basel) 2020;12:2783.
