EPIGENETICS OF GALLBLADDER CANCER: ROLE OF DNA METHYLATION AND HISTONE MODIFICATIONS
Main Article Content
Keywords
Gallbladder, Gallbladder cancer, Epigenetics, DNA methylation, Chromatin modification, Methylation specific PCR
Abstract
Delayed diagnosis and inability to receive benefits from systemic treatment, gallbladder cancer has a worrisome prognosis and has become a major public health concern, worldwide. The precise cause of the occurrence of gallbladder cancer is concealed so far, however, several genetic (mutations), epigenetic (DNA methylation, histone modification), and environmental factors responsible for its causation have been identified. High-throughput techniques now permit an exhaustive study of genetic and epigenetic impairments linked to gallbladder cancer.
The subject of concern in this review is epigenetic regulation, particularly gene methylation, and histone modification, in gallbladder cancer. DNA methylation has evolved as a major molecular mechanism of gallbladder cancer. Different molecular markers have been identified as epigenetically modified in gallbladder cancer. The determination of DNA methylation profile would facilitate biomarkers to be developed for early identification, diagnosis, prognosis and selection of therapies for gall bladder cancer. This review provides an overview on the updated account of the studied made so far on the role of epigenetic modifications in the regulation of tumorigenesis of gallbladder.
References
1. Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer.2004; 4(9):695-706.
2. Shrikhande SV, Barreto SG, Singh S, Udwadia TE, Agarwal AK. Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause. Eur J Surg Oncol. 2010; 36(6):514-519.
3. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006; 118(7):1591-1602.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249.
5. Sharma A, Sharma KL, Gupta A, Yadav A, Kumar . Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol.2017; 23(22):3978-3998.
6. Waddington CH, Waddington CH . The epigenotype. 1942. Int J Epidemiol.2012; 41(1):10-13.
7. Shen L, Kondo Y, Ahmed S, Boumber Y, Konishi K, et al. Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel. Cancer Res. 2007; 67(23):11335-11343.
8. Ducasse M, Brown MA. Epigenetic aberrations and cancer. Mol Cancer. 2006; 5:60.
9. Dehan P, Kustermans G, Guenin S, Horion J, Boniver J, et al. DNA methylation and cancer diagnosis: new methods and applications. Expert Rev Mol Diagn.2009; 9(7):651-657.
10. Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta.2007; 1775(1):138-162.
11. Chervona Y, Costa M.Histone modifications and cancer: biomarkers of prognosis. Am J Cancer Res.2012; 2(5):589-597.
12. Singh AK, Bishayee A, Pandey AK.(Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy. Nutrients.2018; 10(6):E731.
13. Gibney ER, Nolan CM .(Epigenetics and gene expression. Heredity (Edinb). 2010; 105(1):4-13.
14. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, et al. ( Human DNA methylomes at base resolution show widespread epigenomic differences. Nature.2009; 462(7271):315-322.
15. Lu Y, Chan YT, Tan HY, Li S, Wang N, et al. (Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer.2020; 19(1):79.
16. Jones PA, Takai D.The role of DNA methylation in mammalian epigenetics. Science.2001; 293(5532):1068-1070.
17. Bannister AJ, Kouzarides T.Regulation of chromatin by histone modifications. Cell Res.2011; 21(3):381-395.
18. Wiles ET, Selker EU. H3K27 methylation: a promiscuous repressive chromatin mark. Curr Opin Genet Dev.2017; 43:31-37.
19. Wang Z, Schones DE, Zhao K.Characterization of human epigenomes. Curr Opin Genet Dev.2009; 19(2):127-134.
20. Bhaumik SR, Smith E, Shilatifard A. Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol.2007; 14(11):1008-1016.
21. Zhao Z, Shilatifard A . Epigenetic modifications of histones in cancer. Genome Biol.2019; 20(1):245.
22. Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, et al. (The Polycomb group protein EZH2 directly controls DNA methylation. Nature.2006; 439(7078):871-874.
23. Behera G, Mitra S, Mishra TS, Purkait S. ( Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma. J Gastrointest Cancer.2021; 52(3):1029-1034.
24. Liu DC, Yang ZL. (Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma. Pathol Res Pract.2011; 207(8):472-478.
25. Yamaguchi J, Sasaki M, Sato Y, Itatsu K, Harada K, et al. (Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma. Cancer Sci.2010; 101(2):355-362.
26. Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, et al. (A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Bio. 2014; 9(6):1284-1293.
27. Lian SX, Shao YB, Liu HB, He JY, Lu WQ, et al. (Lysine-specific demethylase 1 promotes tumorigenesis and predicts prognosis in gallbladder cancer. Oncotarget .2015; 6(32):33065-33076.
28. Li Y, Seto E.( HDACs and HDAC Inhibitors in Cancer Development and Therapy. Cold Spring Harb Perspect Med.2016; 6(10):a026831.
29. Di Martile M, Del Bufalo D, Trisciuoglio D. (The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target. Oncotarget.2016; 7(34):55789-55810.
30. Hodawadekar SC, Marmorstein R. (Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene.2007; 26(37):5528-5540.
31. Feng FL, Yu Y, Liu C, Zhang BH, Cheng QB, et al. KAT5 silencing induces apoptosis of GBC-SD cells through p38MAPK-mediated upregulation of cleaved Casp9. Int J Clin Exp Pathol.2014; 7(1):80-91.
32. He J, Shen S, Lu W, Zhou Y, Hou Y, et al. HDAC1 promoted migration and invasion binding with TCF12 by promoting EMT progress in gallbladder cancer. Oncotarget.2016; 7(22):32754-32764.
33. Xu LN, Wang X, Zou SQ.Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines. World J Gastroenterol.2008; 14(16):2578-2581.
34. Rossetto D, Truman AW, Kron SJ, Côté J.Epigenetic modifications in double-strand break DNA damage signaling and repair. Clin Cancer Res .2010; 16(18):4543-4552.
35. Qin J, Wen B, Liang Y, Yu W, Li H. Histone Modifications and their Role in Colorectal Cancer (Review). Pathol Oncol Res.2020; 26(4):2023-2033.
36. Dawson MA, Foster SD, Bannister AJ, Robson SC, Hannah R, et al. Three distinct patterns of histone H3Y41 phosphorylation mark active genes. Cell Rep.2012; 2(3):470-477.
37. Hurd PJ, Bannister AJ, Halls K, Dawson MA, Vermeulen M, et al. Phosphorylation of histone H3 Thr-45 is linked to apoptosis. J Biol Chem.2009; 284(24):16575-16583.
38. Sun T, Liu Z, Yang Q.The role of ubiquitination and deubiquitination in cancer metabolism. Mol Cancer.2020; 19(1):146.
39. Mansour MA.Ubiquitination: Friend and foe in cancer. Int J Biochem Cell Biol .2018; 101:80-93.
40. Shiio Y, Eisenman RN.Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A.2003; 100(23):13225-13230.
41. Robertson KD.DNA methylation and human disease. Nat Rev Genet.2005; 6(8):597-610.
42. Cheng X, Blumenthal RM.Mammalian DNA methyltransferases: a structural perspective. Structure.2005; 16(3):341-350.
43. Herman JG, Baylin SB.Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med.2003; 349(21):2042-2054.
44. Wang Y, Leung FC.An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics.2004; 20(7):1170-1177.
45. Ehrlich M.DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics.2019;14(12):1141-1163.
46. Castillo J, García P, & Roa JC. Alteraciones genéticas en lesiones preneoplásicas y neoplásicas de la vesícula biliar [Genetic alterations in preneoplastic and neoplastic injuries of the gallbladder]. Revista medica de Chile.2010; 138(5), 595–604.
47. Duan R, Du W, Guo W.EZH2: a novel target for cancer treatment. J Hematol Oncol.2020; 13(1):104.
48. Liu TP, Lo HL, Wei LS, Hsiao HH, Yang PM.S-Adenosyl-L-methionine-competitive inhibitors of the histone methyltransferase EZH2 induce autophagy and enhance drug sensitivity in cancer cells. Anticancer Drugs.2015; 26(2):139-147.
49. Hirukawa A, Smith HW, Zuo D, Dufour CR, Savage P, et al.Targeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic transcriptional program. Nat Commun.2018; 9(1):2547.
50. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature.2002; 419(6907):624-629.
51. Pan YM, Wang CG, Zhu M, Xing R, Cui JT, et al. STAT3 signaling drives EZH2 transcriptional activation and mediates poor prognosis in gastric cancer. Mol Cancer.2016; 15(1):79.
52. Wang SH, Yang Y, Wu XC, Zhang MD, Weng MZ, et al. Long non-coding RNA MINCR promotes gallbladder cancer progression through stimulating EZH2 expression. Cancer Lett.2016; 380(1):122-133.
53. Behera G, Mitra S, Mishra TS, Purkait S.Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma. J Gastrointest Cancer.2021; 52(3):1029-1034.
54. Sheng S, Truong B, Fredrickson D, Wu R, Pardee AB, et al. Tissue-type plasminogen activator is a target of the tumor suppressor gene maspin. Proc Natl Acad Sci U S A.1998;95(2):499-504.
55. Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, et al. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science.1994; 263(5146):526-529.
56. Maass N, Hojo T, Ueding M, Lüttges J, Klöppel G, et al. Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res.2001; 7(4):812-817.
57. Zou Z, Gao C, Nagaich AK, Connell T, Saito S, et al. p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem.2000; 275(9):6051-6054.
58. Baghel K, Kazmi HR, Chandra A, Raj S, Srivastava RN. Significance of methylation status of MASPIN gene and its protein expression in prognosis of gallbladder cancer. Asia Pac J Clin Oncol.2019; 15(5):e120-e125.
59. Boltze C, Schneider-Stock R, Quednow C, Hinze R, Mawrin C, et al. Silencing of the maspin gene by promoter hypermethylation in thyroid cancer. Int J Mol Med.2003; 12(4):479-484.
60. Maass N, Biallek M, Rösel F, Schem C, Ohike N, et al. Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer. Biochem Biophys Res Commun.2002; 297(1):125-128.
61. Sato N, Fukushima N, Matsubayashi H, Goggins M. Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene.2004; 23(8):1531-1538.
62. Fujisawa K, Maesawa C, Sato R, Wada K, Ogasawara S, et al. Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. Lab Invest.2005; 85(2):214-224.
63. Jeschke J, O'Hagan HM, Zhang W, Vatapalli R, Calmon MF, et al. Frequent inactivation of cysteine dioxygenase type 1 contributes to survival of breast cancer cells and resistance to anthracyclines. Clin Cancer Res.2013; 19(12):3201-3211.
64. Igarashi K, Yamashita K, Katoh H, Kojima K, Ooizumi Y, et al. Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease. PLoS One.2017; 12(11):e0188178.
65. Fujiyama Y, Kumamoto Y, Nishizawa N, Nakamoto S, Harada H, et al. Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN). Ann Surg Oncol.2020; 27(10):4007-4016.
66. Nishizawa N, Harada H, Kumamoto Y, Kaizu T, Katoh H, et al. Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer. Cancer Sci.2019; 110(9):2846-2855.
67. Poggi L, Casarosa S, Carl M. An Eye on the Wnt Inhibitory Factor Wif1. Front Cell Dev Biol.2018; 6:167.
68. Yin A, Korzh V, Gong Z. Perturbation of zebrafish swimbladder development by enhancing Wnt signaling in Wif1 morphants. Biochim Biophys Acta.2012; 1823(2):236-244.
69. Huang Y, Du Q, Wu W, She F, Chen Y. Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins. Mol Med Rep.2016; 14(3):2573-2581.
70. Lin B, Hong H, Jiang X, Li C, Zhu S, et al. c‑Jun suppresses the expression of WNT inhibitory factor 1 through transcriptional regulation and interaction with DNA methyltransferase 1 in gallbladder cancer. Mol Med Rep.2018; 17(6):8180-8188.
71. Huang Y, Du Q, Wu W, She F, Chen Y. Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins. Mol Med Rep.2016; 14(3):2573-2581.
72. Guo H, Zhou S, Tan L, Wu X, Wu Z, et al. Clinicopathological significance of WIF1 hypermethylation in NSCLC, a meta-analysis and literature review. Oncotarget.2017; 8(2):2550-2557.
73. Deng X, Hou C, Wang H, Liang T, Zhu L. Hypermethylation of WIF1 and its inhibitory role in the tumor growth of endometrial adenocarcinoma. Mol Med Rep.2017; 16(5):7497-7503.
74. Freese JL, Pino D, Pleasure SJ. Wnt signaling in development and disease. Neurobiol Dis.2010 ;38(2):148-153.
75. Gondkar K, Patel K, Patil Okaly GV, Nair B, Pandey A, et al. Dickkopf Homolog 3 (DKK3) Acts as a Potential Tumor Suppressor in Gallbladder Cancer. Front Oncol.2019; 9:1121.
76. Liang L, He H, Lv R, Zhang M, Huang H, et al. Preliminary mechanism on the methylation modification of Dkk-1 and Dkk-3 in hepatocellular carcinoma. Tumour Biol.2015; 36(2):1245-1250.
77. Xu Y, Li X, Wang H, Xie P, Yan X, et al. Hypermethylation of CDH13, DKK3 and FOXL2 promoters and the expression of EZH2 in ovary granulosa cell tumors. Mol Med Rep.2016; 14(3):2739-2745.
78. Huang Y, Yang M, Huang W.14-3-3 σ: A potential biomolecule for cancer therapy. Clin Chim.2020; Acta 511:50-58.
79. Yoon NK, Seligson DB, Chia D, Elshimali Y, Sulur G, et al. Higher expression levels of 14-3-3sigma in ductal carcinoma in situ of the breast predict poorer outcome. Cancer Biomark.2009; 5(4):215-224.
80. Sirivatanauksorn V, Dumronggittigule W, Dulnee B, Srisawat C, Sirivatanauksorn Y, et al. Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker. Surg Oncol.2020; 32:57-62.
81. Umbricht CB, Evron E, Gabrielson E, Ferguson A, Marks J, et al. Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer. Oncogene.2001; 20(26):3348-3353.
82. Kunze E, Wendt M, Schlott T.Promoter hypermethylation of the 14-3-3 sigma, SYK and CAGE-1 genes is related to the various phenotypes of urinary bladder carcinomas and associated with progression of transitional cell carcinomas. Int J Mol Med.2006; 18(4):547-557.
83. Nakayama H, Sano T, Motegi A, Oyama T, Nakajima T. Increasing 14-3-3 sigma expression with declining estrogen receptor alpha and estrogen-responsive finger protein expression defines malignant progression of endometrial carcinoma. Pathol Int.2005; 55(11):707-715.
84. Shiba-Ishii A, Noguchi M. Aberrant stratifin overexpression is regulated by tumor-associated CpG demethylation in lung adenocarcinoma. Am J Pathol.2012; 180(4):1653-1662.
85. Letelier P, Brebi P, Tapia O, Roa JC.DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer. Clin Epigenetics.2012; 4(1):11.
86. Xu D, Yuan H, Meng Z, Yang C, Li Z, et al. Cadherin 13 Inhibits Pancreatic Cancer Progression and Epithelial-mesenchymal Transition by Wnt/β-Catenin Signaling. J Cancer.2020; 11(8):2101-2112.
87. Miyamoto K, Asada K, Fukutomi T, Okochi E, Yagi Y, et al. Methylation-associated silencing of heparan sulfate D-glucosaminyl 3-O-sulfotransferase-2 (3-OST-2) in human breast, colon, lung and pancreatic cancers. Oncogene.2003; 22(2):274-280.
88. Hwang JA, Kim Y, Hong SH, Lee J, Cho YG, et al. Epigenetic inactivation of heparan sulfate (glucosamine) 3-O-sulfotransferase 2 in lung cancer and its role in tumorigenesis. PLoS One.2013; 8(11):e79634.
89. Takahashi T, Shivapurkar N, Riquelme E, Shigematsu H, Reddy J, et al. Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res.2004; 10(18 Pt 1):6126-6133
90. Deming SL, Nass SJ, Dickson RB, Trock BJ. C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance. Br J Cancer.2000; 83(12):1688-1695.
91. Ishak G, Leal MF, Dos Santos NP, Demachki S, Nunes CA, et al. Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas. Clin Exp Med.2015;15(3):421-426.
92. Massó-Vallés D, Beaulieu ME, Soucek L.MYC, MYCL, and MYCN as therapeutic targets in lung cancer. Expert Opin Ther Targets.2020; 24(2):101-114.
93. Barry KH, Mohanty K, Erickson PA, Wang D, Shi J, et al. MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score. Genes (Basel).2020; 12(1):E12.
94. Zöchbauer-Müller S, Fong KM, Maitra A, Lam S, Geradts J, et al. 5' CpG island methylation of the IT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Res.2001; 61(9):3581-3585.
95. Greenspan DL, Connolly DC, Wu R, Lei RY, Vogelstein JT, et al. Loss of FHIT expression in cervical carcinoma cell lines and primary tumors. Cancer Res.1997; 57(21):4692-4698.
96. Riquelme E, Tang M, Baez S, Diaz A, Pruyas M, et al. Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma. Cancer Lett.2007; 250(1):100-106.
97. Wistuba II, Ashfaq R, Maitra A, Alvarez H, Riquelme E, et al. Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma. Am J Pathol .2002; 160(6):2073-2079.
98. Yan W, Xu N, Han X, Zhou XM, He B.The clinicopathological significance of FHIT hypermethylation in non-small cell lung cancer, a meta-analysis and literature review. Sci Rep.2016; 6:19303.
99. Zhang Y, Xu X, Chen Z, Zhao Z. Association of FHIT expression and FHIT gene hypermethylation with liver cancer risk: a PRISMA-compliant meta-analysis. Onco Targets Ther.2017; 10:3083-3093.
100. Bin Y, Ding Y, Xiao W, Liao A.RASSF1A: A promising target for the diagnosis and treatment of cancer. Clin Chim Acta.2020; 504:98-108.
101. Hesson LB, Cooper WN, Latif F. The role of RASSF1A methylation in cancer. Dis Markers.2007; 23(1-2):73-87
102. Hagrass HA, Pasha HF, Shaheen MA, Abdel Bary EH, Kassem R. Methylation status and protein expression of RASSF1A in breast cancer patients. Mol Biol Rep.2014; 41(1):57-65.
103. Kee SK, Lee JY, Kim MJ, Lee SM, Jung YW, et al. Hypermethylation of the Ras association domain family 1A (RASSF1A) gene in gallbladder cancer. Mol Cells.2007; 24(3):364-371.
104. Iruela-Arispe ML, Lombardo M, Krutzsch HC, Lawler J, Roberts DD. Inhibition of angiogenesis by thrombospondin-1 is mediated by 2 independent regions within the type 1 repeats. Circulation.1999; 100(13):1423-1431.
105. Liu X, Xu D, Liu Z, Li Y, Zhang C, et al. THBS1 facilitates colorectal liver metastasis through enhancing epithelial-mesenchymal transition. Clin Transl Oncol.2020; 22(10):1730-1740.
106. Horiguchi H, Yamagata S, Rong Qian Z, Kagawa S, Sakashita N. Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis. J Med Invest.2013; 60(1-2):91-96.
107. Pal SK, Nguyen CT, Morita KI, Miki Y, Kayamori K, et al. THBS1 is induced by TGFB1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma. J Oral Pathol Med.2016; 45(10):730-739.
108. Firlej V, Mathieu JR, Gilbert C, Lemonnier L, Nakhlé J, et al.Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res.2017; 71(24):7649-7658.
109. Huang T, Wang L, Liu D, Li P, Xiong H, et al. FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1. Int J Oncol.2017; 50(5):1501-1512.
110. Roh YH, Kim YH, Choi HJ, Lee KE, Roh MS.Fascin overexpression correlates with positive thrombospondin-1 and syndecan-1 expressions and a more aggressive clinical course in patients with gallbladder cancer. J Hepatobiliary Pancreat Surg.2009; 16(3):315-321.
111. Tekcham DS, Gupta S, Shrivastav BR, Tiwari PK . Epigenetic Downregulation of PTEN in Gallbladder Cancer. J Gastrointest Cancer.2017; 48(1):110-116.
112. Luo S, Chen J, Mo X. The association of PTEN hypermethylation and breast cancer: a meta-analysis. Onco Targets Ther .2016; 9:5643-5650.
113. Kadian LK, Yadav R, Nanda S, Gulshan G, Sharma S, et al. High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India. Mol Biol Rep.2020; 47(12):9725-9732.
114. Sparks AB, Morin PJ, Vogelstein B, Kinzler KW..1998; Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 58(6):1130-1134.
115. Takahashi T, Shivapurkar N, Riquelme E, Shigematsu H, Reddy J, et al. Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res.2004; 10(18 Pt 1):6126-6133.
116. Tekcham DS, Poojary SS, Bhunia S, Barbhuiya MA, Gupta S, et al. Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer. Indian J Med Res.2016; 143(Supplement):S82-S90.
117. Saelee P, Pongtheerat T. APC Promoter Hypermethylation as a Prognostic Marker in Breast Cancer Patients. Asian Pac J Cancer.2020; Prev 21(12):3627-3632.
118. Aghabozorgi AS, Bahreyni A, Soleimani A, Bahrami A, Khazaei M, etal. Role of adenomatous polyposis coli (APC) gene mutations in the pathogenesis of colorectal cancer; current status and perspectives. Biochimie.2019; 157:64-71.
119. Heerboth S, Lapinska K, Snyder N, Leary M, Rollinson S, et al. Use of epigenetic drugs in disease: an overview. Genet Epigenet.2014; 6:9-19.
120. Jones PA, Issa JP, Baylin S. Targeting the cancer epigenome for therapy. Nat Rev Genet.2016; 17(10):630-641.
121. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist.2005; 10(3):176-182.
122. Momparler RL. Pharmacology of 5-Aza-2'-deoxycytidine (decitabine). Semin Hematol.2005; 42(3 Suppl 2).2005; S9-16.
123. Santi DV, Norment A, Garrett CE. Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci U S A.1984; 81(22):6993-6997.
124. Kuck D, Caulfield T, Lyko F, Medina-Franco JL. Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells. Mol Cancer Ther.2010; 9(11):3015-3023.
125. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov.2006; 5(9):769-784.
126. Liu S, Li F, Pan L, Yang Z, Shu Y, et al. BRD4 inhibitor and histone deacetylase inhibitor synergistically inhibit the proliferation of gallbladder cancer in vitro and in vivo. Cancer Sci.2019; 110(8):2493-2506.
127. Yang D, Chen T, Zhan M, Xu S, Yin X, et al. Modulation of mTOR and epigenetic pathways as therapeutics in gallbladder cancer. Mol Ther Oncolytics.2021; 20:59-70.
128. Duan YT, Yang XA, Fang LY, Wang JH, Liu Q.Anti-proliferative and anti-invasive effects of garcinol from Garcinia indica on gallbladder carcinoma cells. Pharmazie.2018; 73(7):413-417
129. Wei D, Rui B, Qingquan F, Chen C, Ping HY, et al. KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer. Int J Biol Sci.2021; 17(2):514-526.
130. Kitamura T, Connolly K, Ruffino L, Ajiki T, Lueckgen A, et al. The therapeutic effect of histone deacetylase inhibitor PCI-24781 on gallbladder carcinoma in BK5.erbB2 mice. J Hepatol.2012; 57(1):84-91.
131. Pignochino Y, Sarotto I, Peraldo-Neia C, Penachioni JY, Cavalloni G, et al. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer.2010; 10:631.
132. Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol.2010; 11(1):48-54.
133. Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol.2010; 28(21):3491-3497.
134. Bekaii-Saab T, Phelps MA, Li X, Saji M, Goff L, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol.2011; 29(17):2357-2363
135. Ruch JM, Kim EJ. Hedgehog signaling pathway and cancer therapeutics: progress to date. Drugs.2013; 73(7):613-623.
136. Meiss F, Zeiser R. Vismodegib. Recent Results Cancer Res.2014; 201:405-417.
137. Tremblay MR, Lescarbeau A, Grogan MJ, Tan E, Lin G, et al. Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926). J Med Chem.2009; 52(14):4400-4418.
138. Jia J, Qin Y, Zhang L, Guo C, Wang Y, et al. Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis. Mol Med Rep.2016; 13(5):4461-4468.
139. Yang D, Chen T, Zhan M, Xu S, Yin X, et al. Modulation of mTOR and epigenetic pathways as therapeutics in gallbladder cancer. Mol Ther Oncolytics.2021; 20:59-70.
140. Lv T, Yuan D, Miao X, Lv Y, Zhan P, et al. Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One. 2012; 7(4):e35065.
141. Xie Q, Tang T, Pang J, Xu J, Yang X, et al. LSD1 Promotes Bladder Cancer Progression by Upregulating LEF1 and Enhancing EMT. Front Oncol. 2020; 10:1234.
142.Omarjee S, Carroll JS Targeting LSD1 and FOXA1 in prostate cancer. Nat Genet 2020 ;52(10):1002-1003.
143. Liu Y, Liu H, Luo X, Deng J, Pan Y, et al. Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer. Tumour Biol. 2015; 36(6):4377-4386
144. Giakountis A, Moulos P, Sarris ME, Hatzis P, Talianidis I Smyd3-associated regulatory pathways in cancer. Semin Cancer Biol. 2017; 42:70-80.
145. Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, et al. Enhanced SMYD3 expression is essential for the growth of breast casncer cells. Cancer Sci. 2006; 97(2):113-118.
146 Ono H, Basson MD, Ito H .EP300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer. Oncotarget.2016; 7(32):51301-51310.
147. Ring A, Kaur P, Lang JE. EP300 knockdown reduces cancer stem cell phenotype, tumor growth and metastasis in triple negative breast cancer. BMC Cancer.2020; 20(1):1076.
148. Zou LJ, Xiang QP, Xue XQ, Zhang C, Li CC, et al. Y08197 is a novel and selective CBP/EP300 bromodomain inhibitor for the treatment of prostate cancer. Acta Pharmacol Sin.2019; 40(11):1436-1447.
149. Hirosawa T, Ishida M, Ishii K, Kanehara K, Kudo K, et al. Loss of BAP1 expression is associated with genetic mutation and can predict outcomes in gallbladder cancer. PLoS One.2018; 13(11):e0206643.
150. Qin J, Zhou Z, Chen W, Wang C, Zhang H, et al. BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5. Nat Commun.2015; 6:8471.
151. Brekken RA. Loss of BAP1 Leads to More YAPing in Pancreatic Cancer. Cancer Res.2020; 80(8):1624-1625.
152. Gao Y, Wang Z, Zhu Y, Zhu Q, Yang Y, et al. NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma. Cancer Sci.2019; 110(11):3510-3519.
153. Lu L, Zhu G, Zeng H, Xu Q, Holzmann K. High tRNA Transferase NSUN2 Gene Expression is Associated with Poor Prognosis in Head and Neck Squamous Carcinoma. Cancer Invest.2018 ;36(4):246-253.
2. Shrikhande SV, Barreto SG, Singh S, Udwadia TE, Agarwal AK. Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause. Eur J Surg Oncol. 2010; 36(6):514-519.
3. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006; 118(7):1591-1602.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249.
5. Sharma A, Sharma KL, Gupta A, Yadav A, Kumar . Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol.2017; 23(22):3978-3998.
6. Waddington CH, Waddington CH . The epigenotype. 1942. Int J Epidemiol.2012; 41(1):10-13.
7. Shen L, Kondo Y, Ahmed S, Boumber Y, Konishi K, et al. Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel. Cancer Res. 2007; 67(23):11335-11343.
8. Ducasse M, Brown MA. Epigenetic aberrations and cancer. Mol Cancer. 2006; 5:60.
9. Dehan P, Kustermans G, Guenin S, Horion J, Boniver J, et al. DNA methylation and cancer diagnosis: new methods and applications. Expert Rev Mol Diagn.2009; 9(7):651-657.
10. Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta.2007; 1775(1):138-162.
11. Chervona Y, Costa M.Histone modifications and cancer: biomarkers of prognosis. Am J Cancer Res.2012; 2(5):589-597.
12. Singh AK, Bishayee A, Pandey AK.(Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy. Nutrients.2018; 10(6):E731.
13. Gibney ER, Nolan CM .(Epigenetics and gene expression. Heredity (Edinb). 2010; 105(1):4-13.
14. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, et al. ( Human DNA methylomes at base resolution show widespread epigenomic differences. Nature.2009; 462(7271):315-322.
15. Lu Y, Chan YT, Tan HY, Li S, Wang N, et al. (Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer.2020; 19(1):79.
16. Jones PA, Takai D.The role of DNA methylation in mammalian epigenetics. Science.2001; 293(5532):1068-1070.
17. Bannister AJ, Kouzarides T.Regulation of chromatin by histone modifications. Cell Res.2011; 21(3):381-395.
18. Wiles ET, Selker EU. H3K27 methylation: a promiscuous repressive chromatin mark. Curr Opin Genet Dev.2017; 43:31-37.
19. Wang Z, Schones DE, Zhao K.Characterization of human epigenomes. Curr Opin Genet Dev.2009; 19(2):127-134.
20. Bhaumik SR, Smith E, Shilatifard A. Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol.2007; 14(11):1008-1016.
21. Zhao Z, Shilatifard A . Epigenetic modifications of histones in cancer. Genome Biol.2019; 20(1):245.
22. Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, et al. (The Polycomb group protein EZH2 directly controls DNA methylation. Nature.2006; 439(7078):871-874.
23. Behera G, Mitra S, Mishra TS, Purkait S. ( Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma. J Gastrointest Cancer.2021; 52(3):1029-1034.
24. Liu DC, Yang ZL. (Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma. Pathol Res Pract.2011; 207(8):472-478.
25. Yamaguchi J, Sasaki M, Sato Y, Itatsu K, Harada K, et al. (Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma. Cancer Sci.2010; 101(2):355-362.
26. Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, et al. (A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Bio. 2014; 9(6):1284-1293.
27. Lian SX, Shao YB, Liu HB, He JY, Lu WQ, et al. (Lysine-specific demethylase 1 promotes tumorigenesis and predicts prognosis in gallbladder cancer. Oncotarget .2015; 6(32):33065-33076.
28. Li Y, Seto E.( HDACs and HDAC Inhibitors in Cancer Development and Therapy. Cold Spring Harb Perspect Med.2016; 6(10):a026831.
29. Di Martile M, Del Bufalo D, Trisciuoglio D. (The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target. Oncotarget.2016; 7(34):55789-55810.
30. Hodawadekar SC, Marmorstein R. (Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene.2007; 26(37):5528-5540.
31. Feng FL, Yu Y, Liu C, Zhang BH, Cheng QB, et al. KAT5 silencing induces apoptosis of GBC-SD cells through p38MAPK-mediated upregulation of cleaved Casp9. Int J Clin Exp Pathol.2014; 7(1):80-91.
32. He J, Shen S, Lu W, Zhou Y, Hou Y, et al. HDAC1 promoted migration and invasion binding with TCF12 by promoting EMT progress in gallbladder cancer. Oncotarget.2016; 7(22):32754-32764.
33. Xu LN, Wang X, Zou SQ.Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines. World J Gastroenterol.2008; 14(16):2578-2581.
34. Rossetto D, Truman AW, Kron SJ, Côté J.Epigenetic modifications in double-strand break DNA damage signaling and repair. Clin Cancer Res .2010; 16(18):4543-4552.
35. Qin J, Wen B, Liang Y, Yu W, Li H. Histone Modifications and their Role in Colorectal Cancer (Review). Pathol Oncol Res.2020; 26(4):2023-2033.
36. Dawson MA, Foster SD, Bannister AJ, Robson SC, Hannah R, et al. Three distinct patterns of histone H3Y41 phosphorylation mark active genes. Cell Rep.2012; 2(3):470-477.
37. Hurd PJ, Bannister AJ, Halls K, Dawson MA, Vermeulen M, et al. Phosphorylation of histone H3 Thr-45 is linked to apoptosis. J Biol Chem.2009; 284(24):16575-16583.
38. Sun T, Liu Z, Yang Q.The role of ubiquitination and deubiquitination in cancer metabolism. Mol Cancer.2020; 19(1):146.
39. Mansour MA.Ubiquitination: Friend and foe in cancer. Int J Biochem Cell Biol .2018; 101:80-93.
40. Shiio Y, Eisenman RN.Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A.2003; 100(23):13225-13230.
41. Robertson KD.DNA methylation and human disease. Nat Rev Genet.2005; 6(8):597-610.
42. Cheng X, Blumenthal RM.Mammalian DNA methyltransferases: a structural perspective. Structure.2005; 16(3):341-350.
43. Herman JG, Baylin SB.Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med.2003; 349(21):2042-2054.
44. Wang Y, Leung FC.An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics.2004; 20(7):1170-1177.
45. Ehrlich M.DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics.2019;14(12):1141-1163.
46. Castillo J, García P, & Roa JC. Alteraciones genéticas en lesiones preneoplásicas y neoplásicas de la vesícula biliar [Genetic alterations in preneoplastic and neoplastic injuries of the gallbladder]. Revista medica de Chile.2010; 138(5), 595–604.
47. Duan R, Du W, Guo W.EZH2: a novel target for cancer treatment. J Hematol Oncol.2020; 13(1):104.
48. Liu TP, Lo HL, Wei LS, Hsiao HH, Yang PM.S-Adenosyl-L-methionine-competitive inhibitors of the histone methyltransferase EZH2 induce autophagy and enhance drug sensitivity in cancer cells. Anticancer Drugs.2015; 26(2):139-147.
49. Hirukawa A, Smith HW, Zuo D, Dufour CR, Savage P, et al.Targeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic transcriptional program. Nat Commun.2018; 9(1):2547.
50. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature.2002; 419(6907):624-629.
51. Pan YM, Wang CG, Zhu M, Xing R, Cui JT, et al. STAT3 signaling drives EZH2 transcriptional activation and mediates poor prognosis in gastric cancer. Mol Cancer.2016; 15(1):79.
52. Wang SH, Yang Y, Wu XC, Zhang MD, Weng MZ, et al. Long non-coding RNA MINCR promotes gallbladder cancer progression through stimulating EZH2 expression. Cancer Lett.2016; 380(1):122-133.
53. Behera G, Mitra S, Mishra TS, Purkait S.Enhancer of Zeste Homolog 2 (EZH2) in Malignant Progression of Gallbladder Carcinoma. J Gastrointest Cancer.2021; 52(3):1029-1034.
54. Sheng S, Truong B, Fredrickson D, Wu R, Pardee AB, et al. Tissue-type plasminogen activator is a target of the tumor suppressor gene maspin. Proc Natl Acad Sci U S A.1998;95(2):499-504.
55. Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, et al. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science.1994; 263(5146):526-529.
56. Maass N, Hojo T, Ueding M, Lüttges J, Klöppel G, et al. Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res.2001; 7(4):812-817.
57. Zou Z, Gao C, Nagaich AK, Connell T, Saito S, et al. p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem.2000; 275(9):6051-6054.
58. Baghel K, Kazmi HR, Chandra A, Raj S, Srivastava RN. Significance of methylation status of MASPIN gene and its protein expression in prognosis of gallbladder cancer. Asia Pac J Clin Oncol.2019; 15(5):e120-e125.
59. Boltze C, Schneider-Stock R, Quednow C, Hinze R, Mawrin C, et al. Silencing of the maspin gene by promoter hypermethylation in thyroid cancer. Int J Mol Med.2003; 12(4):479-484.
60. Maass N, Biallek M, Rösel F, Schem C, Ohike N, et al. Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer. Biochem Biophys Res Commun.2002; 297(1):125-128.
61. Sato N, Fukushima N, Matsubayashi H, Goggins M. Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene.2004; 23(8):1531-1538.
62. Fujisawa K, Maesawa C, Sato R, Wada K, Ogasawara S, et al. Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. Lab Invest.2005; 85(2):214-224.
63. Jeschke J, O'Hagan HM, Zhang W, Vatapalli R, Calmon MF, et al. Frequent inactivation of cysteine dioxygenase type 1 contributes to survival of breast cancer cells and resistance to anthracyclines. Clin Cancer Res.2013; 19(12):3201-3211.
64. Igarashi K, Yamashita K, Katoh H, Kojima K, Ooizumi Y, et al. Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease. PLoS One.2017; 12(11):e0188178.
65. Fujiyama Y, Kumamoto Y, Nishizawa N, Nakamoto S, Harada H, et al. Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN). Ann Surg Oncol.2020; 27(10):4007-4016.
66. Nishizawa N, Harada H, Kumamoto Y, Kaizu T, Katoh H, et al. Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer. Cancer Sci.2019; 110(9):2846-2855.
67. Poggi L, Casarosa S, Carl M. An Eye on the Wnt Inhibitory Factor Wif1. Front Cell Dev Biol.2018; 6:167.
68. Yin A, Korzh V, Gong Z. Perturbation of zebrafish swimbladder development by enhancing Wnt signaling in Wif1 morphants. Biochim Biophys Acta.2012; 1823(2):236-244.
69. Huang Y, Du Q, Wu W, She F, Chen Y. Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins. Mol Med Rep.2016; 14(3):2573-2581.
70. Lin B, Hong H, Jiang X, Li C, Zhu S, et al. c‑Jun suppresses the expression of WNT inhibitory factor 1 through transcriptional regulation and interaction with DNA methyltransferase 1 in gallbladder cancer. Mol Med Rep.2018; 17(6):8180-8188.
71. Huang Y, Du Q, Wu W, She F, Chen Y. Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins. Mol Med Rep.2016; 14(3):2573-2581.
72. Guo H, Zhou S, Tan L, Wu X, Wu Z, et al. Clinicopathological significance of WIF1 hypermethylation in NSCLC, a meta-analysis and literature review. Oncotarget.2017; 8(2):2550-2557.
73. Deng X, Hou C, Wang H, Liang T, Zhu L. Hypermethylation of WIF1 and its inhibitory role in the tumor growth of endometrial adenocarcinoma. Mol Med Rep.2017; 16(5):7497-7503.
74. Freese JL, Pino D, Pleasure SJ. Wnt signaling in development and disease. Neurobiol Dis.2010 ;38(2):148-153.
75. Gondkar K, Patel K, Patil Okaly GV, Nair B, Pandey A, et al. Dickkopf Homolog 3 (DKK3) Acts as a Potential Tumor Suppressor in Gallbladder Cancer. Front Oncol.2019; 9:1121.
76. Liang L, He H, Lv R, Zhang M, Huang H, et al. Preliminary mechanism on the methylation modification of Dkk-1 and Dkk-3 in hepatocellular carcinoma. Tumour Biol.2015; 36(2):1245-1250.
77. Xu Y, Li X, Wang H, Xie P, Yan X, et al. Hypermethylation of CDH13, DKK3 and FOXL2 promoters and the expression of EZH2 in ovary granulosa cell tumors. Mol Med Rep.2016; 14(3):2739-2745.
78. Huang Y, Yang M, Huang W.14-3-3 σ: A potential biomolecule for cancer therapy. Clin Chim.2020; Acta 511:50-58.
79. Yoon NK, Seligson DB, Chia D, Elshimali Y, Sulur G, et al. Higher expression levels of 14-3-3sigma in ductal carcinoma in situ of the breast predict poorer outcome. Cancer Biomark.2009; 5(4):215-224.
80. Sirivatanauksorn V, Dumronggittigule W, Dulnee B, Srisawat C, Sirivatanauksorn Y, et al. Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker. Surg Oncol.2020; 32:57-62.
81. Umbricht CB, Evron E, Gabrielson E, Ferguson A, Marks J, et al. Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer. Oncogene.2001; 20(26):3348-3353.
82. Kunze E, Wendt M, Schlott T.Promoter hypermethylation of the 14-3-3 sigma, SYK and CAGE-1 genes is related to the various phenotypes of urinary bladder carcinomas and associated with progression of transitional cell carcinomas. Int J Mol Med.2006; 18(4):547-557.
83. Nakayama H, Sano T, Motegi A, Oyama T, Nakajima T. Increasing 14-3-3 sigma expression with declining estrogen receptor alpha and estrogen-responsive finger protein expression defines malignant progression of endometrial carcinoma. Pathol Int.2005; 55(11):707-715.
84. Shiba-Ishii A, Noguchi M. Aberrant stratifin overexpression is regulated by tumor-associated CpG demethylation in lung adenocarcinoma. Am J Pathol.2012; 180(4):1653-1662.
85. Letelier P, Brebi P, Tapia O, Roa JC.DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer. Clin Epigenetics.2012; 4(1):11.
86. Xu D, Yuan H, Meng Z, Yang C, Li Z, et al. Cadherin 13 Inhibits Pancreatic Cancer Progression and Epithelial-mesenchymal Transition by Wnt/β-Catenin Signaling. J Cancer.2020; 11(8):2101-2112.
87. Miyamoto K, Asada K, Fukutomi T, Okochi E, Yagi Y, et al. Methylation-associated silencing of heparan sulfate D-glucosaminyl 3-O-sulfotransferase-2 (3-OST-2) in human breast, colon, lung and pancreatic cancers. Oncogene.2003; 22(2):274-280.
88. Hwang JA, Kim Y, Hong SH, Lee J, Cho YG, et al. Epigenetic inactivation of heparan sulfate (glucosamine) 3-O-sulfotransferase 2 in lung cancer and its role in tumorigenesis. PLoS One.2013; 8(11):e79634.
89. Takahashi T, Shivapurkar N, Riquelme E, Shigematsu H, Reddy J, et al. Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res.2004; 10(18 Pt 1):6126-6133
90. Deming SL, Nass SJ, Dickson RB, Trock BJ. C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance. Br J Cancer.2000; 83(12):1688-1695.
91. Ishak G, Leal MF, Dos Santos NP, Demachki S, Nunes CA, et al. Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas. Clin Exp Med.2015;15(3):421-426.
92. Massó-Vallés D, Beaulieu ME, Soucek L.MYC, MYCL, and MYCN as therapeutic targets in lung cancer. Expert Opin Ther Targets.2020; 24(2):101-114.
93. Barry KH, Mohanty K, Erickson PA, Wang D, Shi J, et al. MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score. Genes (Basel).2020; 12(1):E12.
94. Zöchbauer-Müller S, Fong KM, Maitra A, Lam S, Geradts J, et al. 5' CpG island methylation of the IT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Res.2001; 61(9):3581-3585.
95. Greenspan DL, Connolly DC, Wu R, Lei RY, Vogelstein JT, et al. Loss of FHIT expression in cervical carcinoma cell lines and primary tumors. Cancer Res.1997; 57(21):4692-4698.
96. Riquelme E, Tang M, Baez S, Diaz A, Pruyas M, et al. Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma. Cancer Lett.2007; 250(1):100-106.
97. Wistuba II, Ashfaq R, Maitra A, Alvarez H, Riquelme E, et al. Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma. Am J Pathol .2002; 160(6):2073-2079.
98. Yan W, Xu N, Han X, Zhou XM, He B.The clinicopathological significance of FHIT hypermethylation in non-small cell lung cancer, a meta-analysis and literature review. Sci Rep.2016; 6:19303.
99. Zhang Y, Xu X, Chen Z, Zhao Z. Association of FHIT expression and FHIT gene hypermethylation with liver cancer risk: a PRISMA-compliant meta-analysis. Onco Targets Ther.2017; 10:3083-3093.
100. Bin Y, Ding Y, Xiao W, Liao A.RASSF1A: A promising target for the diagnosis and treatment of cancer. Clin Chim Acta.2020; 504:98-108.
101. Hesson LB, Cooper WN, Latif F. The role of RASSF1A methylation in cancer. Dis Markers.2007; 23(1-2):73-87
102. Hagrass HA, Pasha HF, Shaheen MA, Abdel Bary EH, Kassem R. Methylation status and protein expression of RASSF1A in breast cancer patients. Mol Biol Rep.2014; 41(1):57-65.
103. Kee SK, Lee JY, Kim MJ, Lee SM, Jung YW, et al. Hypermethylation of the Ras association domain family 1A (RASSF1A) gene in gallbladder cancer. Mol Cells.2007; 24(3):364-371.
104. Iruela-Arispe ML, Lombardo M, Krutzsch HC, Lawler J, Roberts DD. Inhibition of angiogenesis by thrombospondin-1 is mediated by 2 independent regions within the type 1 repeats. Circulation.1999; 100(13):1423-1431.
105. Liu X, Xu D, Liu Z, Li Y, Zhang C, et al. THBS1 facilitates colorectal liver metastasis through enhancing epithelial-mesenchymal transition. Clin Transl Oncol.2020; 22(10):1730-1740.
106. Horiguchi H, Yamagata S, Rong Qian Z, Kagawa S, Sakashita N. Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis. J Med Invest.2013; 60(1-2):91-96.
107. Pal SK, Nguyen CT, Morita KI, Miki Y, Kayamori K, et al. THBS1 is induced by TGFB1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma. J Oral Pathol Med.2016; 45(10):730-739.
108. Firlej V, Mathieu JR, Gilbert C, Lemonnier L, Nakhlé J, et al.Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res.2017; 71(24):7649-7658.
109. Huang T, Wang L, Liu D, Li P, Xiong H, et al. FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1. Int J Oncol.2017; 50(5):1501-1512.
110. Roh YH, Kim YH, Choi HJ, Lee KE, Roh MS.Fascin overexpression correlates with positive thrombospondin-1 and syndecan-1 expressions and a more aggressive clinical course in patients with gallbladder cancer. J Hepatobiliary Pancreat Surg.2009; 16(3):315-321.
111. Tekcham DS, Gupta S, Shrivastav BR, Tiwari PK . Epigenetic Downregulation of PTEN in Gallbladder Cancer. J Gastrointest Cancer.2017; 48(1):110-116.
112. Luo S, Chen J, Mo X. The association of PTEN hypermethylation and breast cancer: a meta-analysis. Onco Targets Ther .2016; 9:5643-5650.
113. Kadian LK, Yadav R, Nanda S, Gulshan G, Sharma S, et al. High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India. Mol Biol Rep.2020; 47(12):9725-9732.
114. Sparks AB, Morin PJ, Vogelstein B, Kinzler KW..1998; Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 58(6):1130-1134.
115. Takahashi T, Shivapurkar N, Riquelme E, Shigematsu H, Reddy J, et al. Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res.2004; 10(18 Pt 1):6126-6133.
116. Tekcham DS, Poojary SS, Bhunia S, Barbhuiya MA, Gupta S, et al. Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer. Indian J Med Res.2016; 143(Supplement):S82-S90.
117. Saelee P, Pongtheerat T. APC Promoter Hypermethylation as a Prognostic Marker in Breast Cancer Patients. Asian Pac J Cancer.2020; Prev 21(12):3627-3632.
118. Aghabozorgi AS, Bahreyni A, Soleimani A, Bahrami A, Khazaei M, etal. Role of adenomatous polyposis coli (APC) gene mutations in the pathogenesis of colorectal cancer; current status and perspectives. Biochimie.2019; 157:64-71.
119. Heerboth S, Lapinska K, Snyder N, Leary M, Rollinson S, et al. Use of epigenetic drugs in disease: an overview. Genet Epigenet.2014; 6:9-19.
120. Jones PA, Issa JP, Baylin S. Targeting the cancer epigenome for therapy. Nat Rev Genet.2016; 17(10):630-641.
121. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist.2005; 10(3):176-182.
122. Momparler RL. Pharmacology of 5-Aza-2'-deoxycytidine (decitabine). Semin Hematol.2005; 42(3 Suppl 2).2005; S9-16.
123. Santi DV, Norment A, Garrett CE. Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci U S A.1984; 81(22):6993-6997.
124. Kuck D, Caulfield T, Lyko F, Medina-Franco JL. Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells. Mol Cancer Ther.2010; 9(11):3015-3023.
125. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov.2006; 5(9):769-784.
126. Liu S, Li F, Pan L, Yang Z, Shu Y, et al. BRD4 inhibitor and histone deacetylase inhibitor synergistically inhibit the proliferation of gallbladder cancer in vitro and in vivo. Cancer Sci.2019; 110(8):2493-2506.
127. Yang D, Chen T, Zhan M, Xu S, Yin X, et al. Modulation of mTOR and epigenetic pathways as therapeutics in gallbladder cancer. Mol Ther Oncolytics.2021; 20:59-70.
128. Duan YT, Yang XA, Fang LY, Wang JH, Liu Q.Anti-proliferative and anti-invasive effects of garcinol from Garcinia indica on gallbladder carcinoma cells. Pharmazie.2018; 73(7):413-417
129. Wei D, Rui B, Qingquan F, Chen C, Ping HY, et al. KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer. Int J Biol Sci.2021; 17(2):514-526.
130. Kitamura T, Connolly K, Ruffino L, Ajiki T, Lueckgen A, et al. The therapeutic effect of histone deacetylase inhibitor PCI-24781 on gallbladder carcinoma in BK5.erbB2 mice. J Hepatol.2012; 57(1):84-91.
131. Pignochino Y, Sarotto I, Peraldo-Neia C, Penachioni JY, Cavalloni G, et al. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer.2010; 10:631.
132. Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol.2010; 11(1):48-54.
133. Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol.2010; 28(21):3491-3497.
134. Bekaii-Saab T, Phelps MA, Li X, Saji M, Goff L, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol.2011; 29(17):2357-2363
135. Ruch JM, Kim EJ. Hedgehog signaling pathway and cancer therapeutics: progress to date. Drugs.2013; 73(7):613-623.
136. Meiss F, Zeiser R. Vismodegib. Recent Results Cancer Res.2014; 201:405-417.
137. Tremblay MR, Lescarbeau A, Grogan MJ, Tan E, Lin G, et al. Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926). J Med Chem.2009; 52(14):4400-4418.
138. Jia J, Qin Y, Zhang L, Guo C, Wang Y, et al. Artemisinin inhibits gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis. Mol Med Rep.2016; 13(5):4461-4468.
139. Yang D, Chen T, Zhan M, Xu S, Yin X, et al. Modulation of mTOR and epigenetic pathways as therapeutics in gallbladder cancer. Mol Ther Oncolytics.2021; 20:59-70.
140. Lv T, Yuan D, Miao X, Lv Y, Zhan P, et al. Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One. 2012; 7(4):e35065.
141. Xie Q, Tang T, Pang J, Xu J, Yang X, et al. LSD1 Promotes Bladder Cancer Progression by Upregulating LEF1 and Enhancing EMT. Front Oncol. 2020; 10:1234.
142.Omarjee S, Carroll JS Targeting LSD1 and FOXA1 in prostate cancer. Nat Genet 2020 ;52(10):1002-1003.
143. Liu Y, Liu H, Luo X, Deng J, Pan Y, et al. Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer. Tumour Biol. 2015; 36(6):4377-4386
144. Giakountis A, Moulos P, Sarris ME, Hatzis P, Talianidis I Smyd3-associated regulatory pathways in cancer. Semin Cancer Biol. 2017; 42:70-80.
145. Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, et al. Enhanced SMYD3 expression is essential for the growth of breast casncer cells. Cancer Sci. 2006; 97(2):113-118.
146 Ono H, Basson MD, Ito H .EP300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer. Oncotarget.2016; 7(32):51301-51310.
147. Ring A, Kaur P, Lang JE. EP300 knockdown reduces cancer stem cell phenotype, tumor growth and metastasis in triple negative breast cancer. BMC Cancer.2020; 20(1):1076.
148. Zou LJ, Xiang QP, Xue XQ, Zhang C, Li CC, et al. Y08197 is a novel and selective CBP/EP300 bromodomain inhibitor for the treatment of prostate cancer. Acta Pharmacol Sin.2019; 40(11):1436-1447.
149. Hirosawa T, Ishida M, Ishii K, Kanehara K, Kudo K, et al. Loss of BAP1 expression is associated with genetic mutation and can predict outcomes in gallbladder cancer. PLoS One.2018; 13(11):e0206643.
150. Qin J, Zhou Z, Chen W, Wang C, Zhang H, et al. BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5. Nat Commun.2015; 6:8471.
151. Brekken RA. Loss of BAP1 Leads to More YAPing in Pancreatic Cancer. Cancer Res.2020; 80(8):1624-1625.
152. Gao Y, Wang Z, Zhu Y, Zhu Q, Yang Y, et al. NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma. Cancer Sci.2019; 110(11):3510-3519.
153. Lu L, Zhu G, Zeng H, Xu Q, Holzmann K. High tRNA Transferase NSUN2 Gene Expression is Associated with Poor Prognosis in Head and Neck Squamous Carcinoma. Cancer Invest.2018 ;36(4):246-253.
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Dec 09, 2022
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Nivedita Sharma, Anjali Tomar, & Pramod Kumar Tiwari. (2022). EPIGENETICS OF GALLBLADDER CANCER: ROLE OF DNA METHYLATION AND HISTONE MODIFICATIONS. Journal of Population Therapeutics and Clinical Pharmacology, 29(04), 5421-5440. https://doi.org/10.53555/z7eg7z79
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Author Biographies
Nivedita Sharma
Centre for Genomics (Molecular and Human Genetics), Jiwaji University, Gwalior, Madhya Pradesh 474 011, India
Anjali Tomar
School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh 474 011, India
Pramod Kumar Tiwari
School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, 474 011, India,
How to Cite
Nivedita Sharma, Anjali Tomar, & Pramod Kumar Tiwari. (2022). EPIGENETICS OF GALLBLADDER CANCER: ROLE OF DNA METHYLATION AND HISTONE MODIFICATIONS. Journal of Population Therapeutics and Clinical Pharmacology, 29(04), 5421-5440. https://doi.org/10.53555/z7eg7z79
