Helicobacter pylori -induced inflammation and epigenetic changes during gastric carcinogenesis

World Journal of Gastroenterology

Volumn 21, Issue 45, 2015, Pages 12742-12756

  Valenzuela, Manuel A ^a   Canales, Jimena ^a   Corvalán, Alejandro H ^a,b   Quest, Andrew F G ^a  

^a UNIVERSITY OF CHILE   (Chile)

^b PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

Author keywords

Epigenetics; Gastric cancer; Helicobacter pylori; Methylation; MicroRNA

Indexed keywords

BACTERIAL ENZYME; CONNEXIN 32; CONNEXIN 43; CYCLIN DEPENDENT KINASE INHIBITOR 2A; GAMMA GLUTAMYLTRANSFERASE; MEMBRANE PROTEIN; MICRORNA; SURVIVIN; TRANSCRIPTION FACTOR GATA 4; TRANSCRIPTION FACTOR GATA 5; TRANSCRIPTION FACTOR RUNX3; UNCLASSIFIED DRUG; UVOMORULIN; VEZATIN; VIRULENCE FACTOR; BACTERIAL PROTEIN; CELL CYCLE PROTEIN; GAMMA GLUTAMYLCYCLOTRANSFERASE; GLYCOPROTEIN; RPRM PROTEIN, HUMAN;

CELL CYCLE REGULATION; CELL JUNCTION; DNA DAMAGE; DNA METHYLATION; DNA REPAIR; EPIGENETICS; GASTRIC MUCOSA; GASTRITIS; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HMHL 1 GENE; HRASLS GENE; HUMAN; LOX GENE; NONHUMAN; PRECANCER; PROMOTER REGION; PROTEIN EXPRESSION; REVIEW; STOMACH CANCER; TFF 2 GENE; TUMOR SUPPRESSOR GENE; ANIMAL; CELL TRANSFORMATION; COMPLICATION; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; HELICOBACTER INFECTIONS; HOST PATHOGEN INTERACTION; METABOLISM; MICROBIOLOGY; PATHOGENICITY; PATHOLOGY; PRECANCEROUS CONDITIONS; STOMACH MUCOSA; STOMACH NEOPLASMS; VIRULENCE;

ANIMALS; BACTERIAL PROTEINS; CELL CYCLE PROTEINS; CELL TRANSFORMATION, NEOPLASTIC; DNA DAMAGE; DNA METHYLATION; EPIGENESIS, GENETIC; GAMMA-GLUTAMYLCYCLOTRANSFERASE; GASTRIC MUCOSA; GASTRITIS; GENE EXPRESSION REGULATION, NEOPLASTIC; GLYCOPROTEINS; HELICOBACTER INFECTIONS; HELICOBACTER PYLORI; HOST-PATHOGEN INTERACTIONS; HUMANS; MICRORNAS; PRECANCEROUS CONDITIONS; STOMACH NEOPLASMS; VIRULENCE;

EID: 84948972903     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v21.i45.12742     Document Type: Review

References (162)

1. Peleteiro B, Bastos A, Ferro A, Lunet N. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig Dis Sci 2014; 59: 1698-1709 [PMID: 24563236]
2. Watari J, Chen N, Amenta PS, Fukui H, Oshima T, Tomita T, Miwa H, Lim KJ, Das KM. Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development. World J Gastroenterol 2014; 20: 5461-5473 [PMID: 24833876 DOI: 10. 3748/wjg. v20. i18. 5461]
3. Liu JB, Wu XM, Cai J, Zhang JY, Zhang JL, Zhou SH, Shi MX, Qiang FL. CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer. World J Gastroenterol 2012; 18: 5129-5134 [PMID: 23049225 DOI: 10. 3748/wjg. v18. i36. 5129]
4. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histoclinical classification. Acta Pathol Microbiol Scand 1965; 64: 31-49 [PMID: 14320675]
5. Handa Y, Saitoh T, Kawaguchi M, Misaka R, Ohno H, Tsai CR, Tani Y, Tsurui M, Yoshida H, Morita S, Midorikawa S, Sanji T. Association of Helicobacter pylori and diffuse type gastric cancer. J Gastroenterol 1996; 31 Suppl 9: 29-32 [PMID: 8959514]
6. Nardone G, Rocco A, Malfertheiner P. Review article: helicobacter pylori and molecular events in precancerous gastric lesions. Aliment Pharmacol Ther 2004; 20: 261-270 [PMID: 15274662 DOI: 10. 1111/j. 1365-2036. 2004. 02075. x]
7. Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology 2007; 133: 659-672 [PMID: 17681184 DOI: 10. 1053/j. gastro. 2007. 06. 026]
8. Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, Aburatani H, Akiyama T, Peek RM, Azuma T, Hatakeyama M. Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene 2007; 26: 4617-4626 [PMID: 17237808 DOI: 10. 1038/sj. onc. 1210251]
9. Kaise M, Yamasaki T, Yonezawa J, Miwa J, Ohta Y, Tajiri H. CpG island hypermethylation of tumor-suppressor genes in H. pyloriinfected non-neoplastic gastric mucosa is linked with gastric cancer risk. Helicobacter 2008; 13: 35-41 [PMID: 18205664 DOI: 10. 1111/ j. 1523-5378. 2008. 00572. x]
10. Nardone G, Compare D, De Colibus P, de Nucci G, Rocco A. Helicobacter pylori and epigenetic mechanisms underlying gastric carcinogenesis. Dig Dis 2007; 25: 225-229 [PMID: 17827945 DOI: 10. 1159/000103890]
11. Peek RM, Crabtree JE. Helicobacter infection and gastric neoplasia. J Pathol 2006; 208: 233-248 [PMID: 16362989 DOI: 10. 1002/ path. 1868]
12. Hirahara K, Poholek A, Vahedi G, Laurence A, Kanno Y, Milner JD, O'Shea JJ. Mechanisms underlying helper T-cell plasticity: implications for immune-mediated disease. J Allergy Clin Immunol 2013; 131: 1276-1287 [PMID: 23622118 DOI: 10. 1016/ j. jaci. 2013. 03. 015]
13. Yasmin R, Siraj S, Hassan A, Khan AR, Abbasi R, Ahmad N. Epigenetic regulation of inflammatory cytokines and associated genes in human malignancies. Mediators Inflamm 2015; 2015: 201703 [PMID: 25814785 DOI: 10. 1155/2015/201703]
14. Kawanishi S, Hiraku Y, Pinlaor S, Ma N. Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis. Biol Chem 2006; 387: 365-372 [PMID: 16606333 DOI: 10. 1515/BC. 2006. 049]
15. Fernandes JV, Cobucci RN, Jatobá CA, Fernandes TA, de Azevedo JW, de Araújo JM. The role of the mediators of inflammation in cancer development. Pathol Oncol Res 2015; 21: 527-534 [PMID: 25740073 DOI: 10. 1007/s12253-015-9913-z]
16. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000; 404: 398-402 [PMID: 10746728 DOI: 10. 1038/35006081]
17. Sugimoto M, Furuta T, Shirai N, Nakamura A, Xiao F, Kajimura M, Sugimura H, Hishida A. Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer. J Gastroenterol Hepatol 2007; 22: 51-59 [PMID: 17201881 DOI: 10. 1111/j. 1440-1746. 2006. 04442. x]
18. Taguchi A, Ohmiya N, Shirai K, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, Goto H. Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomarkers Prev 2005; 14: 2487-2493 [PMID: 16284368 DOI: 10. 1158/1055-9965. EPI-05-0326]
19. Zabaleta J, Camargo MC, Piazuelo MB, Fontham E, Schneider BG, Sicinschi LA, Ferrante W, Balart L, Correa P, Ochoa AC. Association of interleukin-1beta gene polymorphisms with precancerous gastric lesions in African Americans and Caucasians. Am J Gastroenterol 2006; 101: 163-171 [PMID: 16405550 DOI: 10. 1111/j. 1572-0241. 2006. 00387. x]
20. Na HK, Woo JH. Helicobacter pylori Induces Hypermethylation of CpG Islands Through Upregulation of DNA Methyltransferase: Possible Involvement of Reactive Oxygen/Nitrogen Species. J Cancer Prev 2014; 19: 259-264 [PMID: 25574460 DOI: 10. 15430/ JCP. 2014. 19. 4. 259]
21. Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, Ichinose M, Tatematsu M, Ushijima T. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res 2010; 70: 1430-1440 [PMID: 20124475 DOI: 10. 1158/0008-5472. CAN-09-2755]
22. Niwa T, Toyoda T, Tsukamoto T, Mori A, Tatematsu M, Ushijima T. Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent. Cancer Prev Res (Phila) 2013; 6: 263-270 [PMID: 23559452 DOI: 10. 1158/1940-6207. CAPR-12-0369]
23. Schneider BG, Piazuelo MB, Sicinschi LA, Mera R, Peng DF, Roa JC, Romero-Gallo J, Delgado AG, de Sablet T, Bravo LE, Wilson KT, El-Rifai W, Peek RM, Correa P. Virulence of infecting Helicobacter pylori strains and intensity of mononuclear cell infiltration are associated with levels of DNA hypermethylation in gastric mucosae. Epigenetics 2013; 8: 1153-1161 [PMID: 24128875 DOI: 10. 4161/epi. 26072]
24. Katayama Y, Takahashi M, Kuwayama H. Helicobacter pylori causes runx3 gene methylation and its loss of expression in gastric epithelial cells, which is mediated by nitric oxide produced by macrophages. Biochem Biophys Res Commun 2009; 388: 496-500 [PMID: 19665002 DOI: 10. 1016/j. bbrc. 2009. 08. 003]
25. Huang FY, Chan AO, Rashid A, Wong DK, Cho CH, Yuen MF. Helicobacter pylori induces promoter methylation of E-cadherin via interleukin-1? activation of nitric oxide production in gastric cancer cells. Cancer 2012; 118: 4969-4980 [PMID: 22415887 DOI: 10. 1002/cncr. 27519]
26. Huang FY, Chan AO, Lo RC, Rashid A, Wong DK, Cho CH, Lai CL, Yuen MF. Characterization of interleukin-1? in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1(-/-)) mice. Eur J Cancer 2013; 49: 2760-2770 [PMID: 23664095 DOI: 10. 1016/ j. ejca. 2013. 03. 031]
27. Nam KT, Oh SY, Ahn B, Kim YB, Jang DD, Yang KH, Hahm KB, Kim DY. Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase. Gut 2004; 53: 1250-1255 [PMID: 15306579 DOI: 10. 1136/ gut. 2003. 030684]
28. Ushijima T, Hattori N. Molecular pathways: involvement of Helicobacter pylori-triggered inflammation in the formation of an epigenetic field defect, and its usefulness as cancer risk and exposure markers. Clin Cancer Res 2012; 18: 923-929 [PMID: 22205689 DOI: 10. 1158/1078-0432. CCR-11-2011]
29. Gonda TA, Kim YI, Salas MC, Gamble MV, Shibata W, Muthupalani S, Sohn KJ, Abrams JA, Fox JG, Wang TC, Tycko B. Folic acid increases global DNA methylation and reduces inflammation to prevent Helicobacter-associated gastric cancer in mice. Gastroenterology 2012; 142: 824-833. e7 [PMID: 22248660 DOI: 10. 1053/j. gastro. 2011. 12. 058]
30. Akhavan-Niaki H, Samadani AA. Molecular insight in gastric cancer induction: an overview of cancer stemness genes. Cell Biochem Biophys 2014; 68: 463-473 [PMID: 24078401 DOI: 10. 1007/s12013-013-9749-7]
31. Handa O, Naito Y, Yoshikawa T. Helicobacter pylori: a ROSinducing bacterial species in the stomach. Inflamm Res 2010; 59: 997-1003 [PMID: 20820854 DOI: 10. 1007/s00011-010-0245-x]
32. Davies GR, Simmonds NJ, Stevens TR, Sheaff MT, Banatvala N, Laurenson IF, Blake DR, Rampton DS. Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut 1994; 35: 179-185 [PMID: 8307467]
33. Touati E, Michel V, Thiberge JM, Wuscher N, Huerre M, Labigne A. Chronic Helicobacter pylori infections induce gastric mutations in mice. Gastroenterology 2003; 124: 1408-1419 [PMID: 12730880]
34. Ma N, Adachi Y, Hiraku Y, Horiki N, Horiike S, Imoto I, Pinlaor S, Murata M, Semba R, Kawanishi S. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection. Biochem Biophys Res Commun 2004; 319: 506-510 [PMID: 15178435 DOI: 10. 1016/j. bbrc. 2004. 04. 193]
35. Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, Azuma T, Okazaki IM, Honjo T, Chiba T. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med 2007; 13: 470-476 [PMID: 17401375 DOI: 10. 1038/nm1566]
36. Shimizu T, Marusawa H, Matsumoto Y, Inuzuka T, Ikeda A, Fujii Y, Minamiguchi S, Miyamoto S, Kou T, Sakai Y, Crabtree JE, Chiba T. Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection. Gastroenterology 2014; 147: 407-417. e3 [PMID: 24786892 DOI: 10. 1053/j. gastro. 2014. 04. 036]
37. Yanaka A. Sulforaphane enhances protection and repair of gastric mucosa against oxidative stress in vitro, and demonstrates antiinflammatory effects on Helicobacter pylori-infected gastric mucosae in mice and human subjects. Curr Pharm Des 2011; 17: 1532-1540 [PMID: 21548875]
38. Drake IM, Davies MJ, Mapstone NP, Dixon MF, Schorah CJ, White KL, Chalmers DM, Axon AT. Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals. Carcinogenesis 1996; 17: 559-562 [PMID: 8631145]
39. Weitzman SA, Turk PW, Milkowski DH, Kozlowski K. Free radical adducts induce alterations in DNA cytosine methylation. Proc Natl Acad Sci USA 1994; 91: 1261-1264 [PMID: 8108398]
40. Sitaraman R. Helicobacter pylori DNA methyltransferases and the epigenetic field effect in cancerization. Front Microbiol 2014; 5: 115 [PMID: 24723914 DOI: 10. 3389/fmicb. 2014. 00115]
41. Krebes J, Morgan RD, Bunk B, Spröer C, Luong K, Parusel R, Anton BP, König C, Josenhans C, Overmann J, Roberts RJ, Korlach J, Suerbaum S. The complex methylome of the human gastric pathogen Helicobacter pylori. Nucleic Acids Res 2014; 42: 2415-2432 [PMID: 24302578 DOI: 10. 1093/nar/gkt1201]
42. Terradot L, Waksman G. Architecture of the Helicobacter pylori Cag-type IV secretion system. FEBS J 2011; 278: 1213-1222 [PMID: 21352491 DOI: 10. 1111/j. 1742-4658. 2011. 08037. x]
43. Backert S, Schwarz T, Miehlke S, Kirsch C, Sommer C, Kwok T, Gerhard M, Goebel UB, Lehn N, Koenig W, Meyer TF. Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer. Infect Immun 2004; 72: 1043-1056 [PMID: 14742552]
44. Glocker E, Lange C, Covacci A, Bereswill S, Kist M, Pahl HL. Proteins encoded by the cag pathogenicity island of Helicobacter pylori are required for NF-kappaB activation. Infect Immun 1998; 66: 2346-2348 [PMID: 9573128]
45. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 2004; 5: 1166-1174 [PMID: 15489856 DOI: 10. 1038/ni1131]
46. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M. Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology 1998; 115: 642-648 [PMID: 9721161]
47. Franco AT, Israel DA, Washington MK, Krishna U, Fox JG, Rogers AB, Neish AS, Collier-Hyams L, Perez-Perez GI, Hatakeyama M, Whitehead R, Gaus K, O'Brien DP, Romero-Gallo J, Peek RM. Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc Natl Acad Sci USA 2005; 102: 10646-10651 [PMID: 16027366 DOI: 10. 1073/pnas. 0504927102]
48. Suarez G, Romero-Gallo J, Piazuelo MB, Wang G, Maier RJ, Forsberg LS, Azadi P, Gomez MA, Correa P, Peek RM. Modification of Helicobacter pylori Peptidoglycan Enhances NOD1 Activation and Promotes Cancer of the Stomach. Cancer Res 2015; 75: 1749-1759 [PMID: 25732381 DOI: 10. 1158/0008-5472. CAN-14-2291]
49. Wang G, Maier SE, Lo LF, Maier G, Dosi S, Maier RJ. Peptidoglycan deacetylation in Helicobacter pylori contributes to bacterial survival by mitigating host immune responses. Infect Immun 2010; 78: 4660-4666 [PMID: 20805339 DOI: 10. 1128/ IAI. 00307-10]
50. Perez-Perez GI, Peek RM, Legath AJ, Heine PR, Graff LB. The role of CagA status in gastric and extragastric complications of Helicobacter pylori. J Physiol Pharmacol 1999; 50: 833-845 [PMID: 10695563]
51. Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, Imanishi J. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains. Gut 1997; 41: 442-451 [PMID: 9391240]
52. Wu J, Xu S, Zhu Y. Helicobacter pylori CagA: a critical destroyer of the gastric epithelial barrier. Dig Dis Sci 2013; 58: 1830-1837 [PMID: 23423500 DOI: 10. 1007/s10620-013-2589-x]
53. Hatakeyama M. Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 2004; 4: 688-694 [PMID: 15343275 DOI: 10. 1038/nrc1433]
54. Azuma T, Yamazaki S, Yamakawa A, Ohtani M, Muramatsu A, Suto H, Ito Y, Dojo M, Yamazaki Y, Kuriyama M, Keida Y, Higashi H, Hatakeyama M. Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 2004; 189: 820-827 [PMID: 14976598 DOI: 10. 1086/381782]
55. Zhu Y, Zhong X, Zheng S, Du Q, Xu W. Transformed immortalized gastric epithelial cells by virulence factor CagA of Helicobacter pylori through Erk mitogen-activated protein kinase pathway. Oncogene 2005; 24: 3886-3895 [PMID: 15856031 DOI: 10. 1038/ sj. onc. 1208551]
56. Bessède E, Staedel C, Acuña Amador LA, Nguyen PH, Chambonnier L, Hatakeyama M, Belleannée G, Mégraud F, Varon C. Helicobacter pylori generates cells with cancer stem cell properties via epithelial-mesenchymal transition-like changes. Oncogene 2014; 33: 4123-4131 [PMID: 24096479 DOI: 10. 1038/onc. 2013. 380]
57. Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 2003; 300: 1430-1434 [PMID: 12775840 DOI: 10. 1126/science. 1081919]
58. Iwamoto J, Mizokami Y, Takahashi K, Nakajima K, Ohtsubo T, Miura S, Narasaka T, Takeyama H, Omata T, Shimokobe K, Ito M, Takehara H, Matsuoka T. Expressions of urokinase-type plasminogen activator, its receptor and plasminogen activator inhibitor-1 in gastric cancer cells and effects of Helicobacter pylori. Scand J Gastroenterol 2005; 40: 783-793 [PMID: 16109653 DOI: 10. 1080/00365520510015665]
59. Wandler AM, Guillemin K. Transgenic expression of the Helicobacter pylori virulence factor CagA promotes apoptosis or tumorigenesis through JNK activation in Drosophila. PLoS Pathog 2012; 8: e1002939 [PMID: 23093933 DOI: 10. 1371/journal. ppat. 1002939]
60. Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, Yamada G, Azuma T, Hatakeyama M. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA 2008; 105: 1003-1008 [PMID: 18192401 DOI: 10. 1073/pnas. 0711183105]
61. Hatakeyama M, Higashi H. Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis. Cancer Sci 2005; 96: 835-843 [PMID: 16367902 DOI: 10. 1111/j. 1349-7006. 2005. 00130. x]
62. Backert S, Tegtmeyer N, Selbach M. The versatility of Helicobacter pylori CagA effector protein functions: The master key hypothesis. Helicobacter 2010; 15: 163-176 [PMID: 20557357 DOI: 10. 1111/ j. 1523-5378. 2010. 00759. x]
63. Backert S, Moese S, Selbach M, Brinkmann V, Meyer TF. Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells. Mol Microbiol 2001; 42: 631-644 [PMID: 11722731]
64. Botham CM, Wandler AM, Guillemin K. A transgenic Drosophila model demonstrates that the Helicobacter pylori CagA protein functions as a eukaryotic Gab adaptor. PLoS Pathog 2008; 4: e1000064 [PMID: 18483552 DOI: 10. 1371/journal. ppat. 1000064]
65. Hatakeyama M. Helicobacter pylori and gastric carcinogenesis. J Gastroenterol 2009; 44: 239-248 [PMID: 19271114 DOI: 10. 1007/ s00535-009-0014-1]
66. Brandt S, Kwok T, Hartig R, König W, Backert S. NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci USA 2005; 102: 9300-9305 [PMID: 15972330 DOI: 10. 1073/pnas. 0409873102]
67. Lamb A, Yang XD, Tsang YH, Li JD, Higashi H, Hatakeyama M, Peek RM, Blanke SR, Chen LF. Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination. EMBO Rep 2009; 10: 1242-1249 [PMID: 19820695 DOI: 10. 1038/embor. 2009. 210]
68. Sepulveda AR, Yao Y, Yan W, Park DI, Kim JJ, Gooding W, Abudayyeh S, Graham DY. CpG methylation and reduced expression of O6-methylguanine DNA methyltransferase is associated with Helicobacter pylori infection. Gastroenterology 2010; 138: 1836-1844 [PMID: 20044995 DOI: 10. 1053/j. gastro. 2009. 12. 042]
69. Hayashi Y, Tsujii M, Wang J, Kondo J, Akasaka T, Jin Y, Li W, Nakamura T, Nishida T, Iijima H, Tsuji S, Kawano S, Hayashi N, Takehara T. CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis. Gut 2013; 62: 1536-1546 [PMID: 22936674 DOI: 10. 1136/ gutjnl-2011-301625]
70. de Bernard M, Moschioni M, Papini E, Telford J, Rappuoli R, Montecucco C. Cell vacuolization induced by Helicobacter pylori VacA toxin: cell line sensitivity and quantitative estimation. Toxicol Lett 1998; 99: 109-115 [PMID: 9817082]
71. de Bernard M, Arico B, Papini E, Rizzuto R, Grandi G, Rappuoli R, Montecucco C. Helicobacter pylori toxin VacA induces vacuole formation by acting in the cell cytosol. Mol Microbiol 1997; 26: 665-674 [PMID: 9427397]
72. Galmiche A, Rassow J, Doye A, Cagnol S, Chambard JC, Contamin S, de Thillot V, Just I, Ricci V, Solcia E, Van Obberghen E, Boquet P. The N-terminal 34 kDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c release. EMBO J 2000; 19: 6361-6370 [PMID: 11101509 DOI: 10. 1093/ emboj/19. 23. 6361]
73. Torres VJ, VanCompernolle SE, Sundrud MS, Unutmaz D, Cover TL. Helicobacter pylori vacuolating cytotoxin inhibits activationinduced proliferation of human T and B lymphocyte subsets. J Immunol 2007; 179: 5433-5440 [PMID: 17911630]
74. Terebiznik MR, Raju D, Vázquez CL, Torbricki K, Kulkarni R, Blanke SR, Yoshimori T, Colombo MI, Jones NL. Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells. Autophagy 2009; 5: 370-379 [PMID: 19164948]
75. Lu H, Yamaoka Y, Graham DY. Helicobacter pylori virulence factors: facts and fantasies. Curr Opin Gastroenterol 2005; 21: 653-659 [PMID: 16220040]
76. Supajatura V, Ushio H, Wada A, Yahiro K, Okumura K, Ogawa H, Hirayama T, Ra C. Cutting edge: VacA, a vacuolating cytotoxin of Helicobacter pylori, directly activates mast cells for migration and production of proinflammatory cytokines. J Immunol 2002; 168: 2603-2607 [PMID: 11884423]
77. Salama NR, Otto G, Tompkins L, Falkow S. Vacuolating cytotoxin of Helicobacter pylori plays a role during colonization in a mouse model of infection. Infect Immun 2001; 69: 730-736 [PMID: 11159961 DOI: 10. 1128/IAI. 69. 2. 730-736. 2001]
78. Atherton JC, Cao P, Peek RM, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 1995; 270: 17771-17777 [PMID: 7629077]
79. Rhead JL, Letley DP, Mohammadi M, Hussein N, Mohagheghi MA, Eshagh Hosseini M, Atherton JC. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology 2007; 133: 926-936 [PMID: 17854597 DOI: 10. 1053/j. gastro. 2007. 06. 056]
80. Winter JA, Letley DP, Cook KW, Rhead JL, Zaitoun AA, Ingram RJ, Amilon KR, Croxall NJ, Kaye PV, Robinson K, Atherton JC. A role for the vacuolating cytotoxin, VacA, in colonization and Helicobacter pylori-induced metaplasia in the stomach. J Infect Dis 2014; 210: 954-963 [PMID: 24625807 DOI: 10. 1093/infdis/jiu154]
81. Sun J, Aoki K, Zheng JX, Su BZ, Ouyang XH, Misumi J. Effect of NaCl and Helicobacter pylori vacuolating cytotoxin on cytokine expression and viability. World J Gastroenterol 2006; 12: 2174-2180 [PMID: 16610017]
82. Sugimoto M, Furuta T, Yamaoka Y. Influence of inflammatory cytokine polymorphisms on eradication rates of Helicobacter pylori. J Gastroenterol Hepatol 2009; 24: 1725-1732 [PMID: 20136959 DOI: 10. 1111/j. 1440-1746. 2009. 06047. x]
83. Cech TR, Steitz JA. The noncoding RNA revolution-trashing old rules to forge new ones. Cell 2014; 157: 77-94 [PMID: 24679528 DOI: 10. 1016/j. cell. 2014. 03. 008]
84. Mikeska T, Craig JM. DNA methylation biomarkers: cancer and beyond. Genes (Basel) 2014; 5: 821-864 [PMID: 25229548 DOI: 10. 3390/genes5030821]
85. Qu Y, Dang S, Hou P. Gene methylation in gastric cancer. Clin Chim Acta 2013; 424: 53-65 [PMID: 23669186 DOI: 10. 1016/ j. cca. 2013. 05. 002]
86. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014; 513: 202-209 [PMID: 25079317 DOI: 10. 1038/nature13480]
87. Kang GH, Shim YH, Jung HY, Kim WH, Ro JY, Rhyu MG. CpG island methylation in premalignant stages of gastric carcinoma. Cancer Res 2001; 61: 2847-2851 [PMID: 11306456]
88. Park SY, Yoo EJ, Cho NY, Kim N, Kang GH. Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection. J Pathol 2009; 219: 410-416 [PMID: 19639607 DOI: 10. 1002/path. 2596]
89. Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, Hui WM, Rashid A, Kwong YL. Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut 2003; 52: 502-506 [PMID: 12631658]
90. Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M, Tamura G, Saito D, Sugimura T, Ichinose M, Ushijima T. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 2006; 12: 989-995 [PMID: 16467114 DOI: 10. 1158/1078-0432. CCR-05-2096]
91. Leung WK, Man EP, Yu J, Go MY, To KF, Yamaoka Y, Cheng VY, Ng EK, Sung JJ. Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach. Clin Cancer Res 2006; 12: 3216-3221 [PMID: 16707623 DOI: 10. 1158/1078-0432. CCR-05-2442]
92. Ushijima T, Nakajima T, Maekita T. DNA methylation as a marker for the past and future. J Gastroenterol 2006; 41: 401-407 [PMID: 16799880 DOI: 10. 1007/s00535-006-1846-6]
93. Perri F, Cotugno R, Piepoli A, Merla A, Quitadamo M, Gentile A, Pilotto A, Annese V, Andriulli A. Aberrant DNA methylation in nonneoplastic gastric mucosa of H. Pylori infected patients and effect of eradication. Am J Gastroenterol 2007; 102: 1361-1371 [PMID: 17509026 DOI: 10. 1111/j. 1572-0241. 2007. 01284. x]
94. Miao R, Guo X, Zhi Q, Shi Y, Li L, Mao X, Zhang L, Li C. VEZT, a novel putative tumor suppressor, suppresses the growth and tumorigenicity of gastric cancer. PLoS One 2013; 8: e74409 [PMID: 24069310 DOI: 10. 1371/journal. pone. 0074409]
95. Me?e G, Richard G, White TW. Gap junctions: basic structure and function. J Invest Dermatol 2007; 127: 2516-2524 [PMID: 17934503 DOI: 10. 1038/sj. jid. 5700770]
96. Wang Y, Huang LH, Xu CX, Xiao J, Zhou L, Cao D, Liu XM, Qi Y. Connexin 32 and 43 promoter methylation in Helicobacter pyloriassociated gastric tumorigenesis. World J Gastroenterol 2014; 20: 11770-11779 [PMID: 25206281 DOI: 10. 3748/wjg. v20. i33. 11770]
97. Alvarez MC, Santos JC, Maniezzo N, Ladeira MS, da Silva AL, Scaletsky IC, Pedrazzoli J, Ribeiro ML. MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults. World J Gastroenterol 2013; 19: 3043-3051 [PMID: 23716983 DOI: 10. 3748/wjg. v19. i20. 3043]
98. Farrell JJ, Taupin D, Koh TJ, Chen D, Zhao CM, Podolsky DK, Wang TC. TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury. J Clin Invest 2002; 109: 193-204 [PMID: 11805131 DOI: 10. 1172/JCI12529]
99. Kurt-Jones EA, Cao L, Sandor F, Rogers AB, Whary MT, Nambiar PR, Cerny A, Bowen G, Yan J, Takaishi S, Chi AL, Reed G, Houghton J, Fox JG, Wang TC. Trefoil family factor 2 is expressed in murine gastric and immune cells and controls both gastrointestinal inflammation and systemic immune responses. Infect Immun 2007; 75: 471-480 [PMID: 17101660 DOI: 10. 1128/IAI. 02039-05]
100. Peterson AJ, Menheniott TR, O'Connor L, Walduck AK, Fox JG, Kawakami K, Minamoto T, Ong EK, Wang TC, Judd LM, Giraud AS. Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans. Gastroenterology 2010; 139: 2005-2017 [PMID: 20801119 DOI: 10. 1053/j. gastro. 2010. 08. 043]
101. Yamada C, Ozaki T, Ando K, Suenaga Y, Inoue K, Ito Y, Okoshi R, Kageyama H, Kimura H, Miyazaki M, Nakagawara A. RUNX3 modulates DNA damage-mediated phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53. J Biol Chem 2010; 285: 16693-16703 [PMID: 20353948 DOI: 10. 1074/ jbc. M109. 055525]
102. Chen W, Gao N, Shen Y, Cen JN. Hypermethylation downregulates Runx3 gene expression and its restoration suppresses gastric epithelial cell growth by inducing p27 and caspase3 in human gastric cancer. J Gastroenterol Hepatol 2010; 25: 823-831 [PMID: 20492341 DOI: 10. 1111/j. 1440-1746. 2009. 06191. x]
103. Lu XX, Yu JL, Ying LS, Han J, Wang S, Yu QM, Wang XB, Fang XH, Ling ZQ. Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression. Cancer 2012; 118: 5507-5517 [PMID: 22576578 DOI: 10. 1002/cncr. 27604]
104. Cheng AS, Li MS, Kang W, Cheng VY, Chou JL, Lau SS, Go MY, Lee CC, Ling TK, Ng EK, Yu J, Huang TH, To KF, Chan MW, Sung JJ, Chan FK. Helicobacter pylori causes epigenetic dysregulation of FOXD3 to promote gastric carcinogenesis. Gastroenterology 2013; 144: 122-133. e9 [PMID: 23058321 DOI: 10. 1053/ j. gastro. 2012. 10. 002]
105. Corre S, Galibert MD. Upstream stimulating factors: highly versatile stress-responsive transcription factors. Pigment Cell Res 2005; 18: 337-348 [PMID: 16162174 DOI: 10. 1111/j. 1600-0749. 2005. 00262. x]
106. Bussière FI, Michel V, Mémet S, Avé P, Vivas JR, Huerre M, Touati E. H. pylori-induced promoter hypermethylation downregulates USF1 and USF2 transcription factor gene expression. Cell Microbiol 2010; 12: 1124-1133 [PMID: 20180799 DOI: 10. 1111/ j. 1462-5822. 2010. 01457. x]
107. Wen XZ, Akiyama Y, Pan KF, Liu ZJ, Lu ZM, Zhou J, Gu LK, Dong CX, Zhu BD, Ji JF, You WC, Deng DJ. Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas. World J Gastroenterol 2010; 16: 1201-1208 [PMID: 20222162]
108. Vadlamudi RK, Li F, Barnes CJ, Bagheri-Yarmand R, Kumar R. p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate. EMBO Rep 2004; 5: 154-160 [PMID: 14749719 DOI: 10. 1038/sj. embor. 7400079]
109. Yan J, Zhang M, Zhang J, Chen X, Zhang X. Helicobacter pylori infection promotes methylation of WWOX gene in human gastric cancer. Biochem Biophys Res Commun 2011; 408: 99-102 [PMID: 21466786 DOI: 10. 1016/j. bbrc. 2011. 03. 127]
110. Kang C, Song JJ, Lee J, Kim MY. Epigenetics: an emerging player in gastric cancer. World J Gastroenterol 2014; 20: 6433-6447 [PMID: 24914365 DOI: 10. 3748/wjg. v20. i21. 6433]
111. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010; 11: 597-610 [PMID: 20661255 DOI: 10. 1038/nrg2843]
112. Stahlhut Espinosa CE, Slack FJ. The role of microRNAs in cancer. Yale J Biol Med 2006; 79: 131-140 [PMID: 17940623]
113. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834-838 [PMID: 15944708 DOI: 10. 1038/nature03702]
114. Vickers KC, Rye KA, Tabet F. MicroRNAs in the onset and development of cardiovascular disease. Clin Sci (Lond) 2014; 126: 183-194 [PMID: 24102098 DOI: 10. 1042/CS20130203]
115. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999-3004 [PMID: 14973191 DOI: 10. 1073/pnas. 0307323101]
116. Raisch J, Darfeuille-Michaud A, Nguyen HT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol 2013; 19: 2985-2996 [PMID: 23716978 DOI: 10. 3748/wjg. v19. i20. 2985]
117. Zhai H, Fesler A, Ju J. MicroRNA: a third dimension in autophagy. Cell Cycle 2013; 12: 246-250 [PMID: 23255136 DOI: 10. 4161/ cc. 23273]
118. Zhang J, Ma L. MicroRNA control of epithelial-mesenchymal transition and metastasis. Cancer Metastasis Rev 2012; 31: 653-662 [PMID: 22684369 DOI: 10. 1007/s10555-012-9368-6]
119. Eulalio A, Schulte L, Vogel J. The mammalian microRNA response to bacterial infections. RNA Biol 2012; 9: 742-750 [PMID: 22664920 DOI: 10. 4161/rna. 20018]
120. Tong F, Cao P, Yin Y, Xia S, Lai R, Liu S. MicroRNAs in gastric cancer: from benchtop to bedside. Dig Dis Sci 2014; 59: 24-30 [PMID: 24114043 DOI: 10. 1007/s10620-013-2887-3]
121. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, Yoshida K, Sasaki H, Nomura S, Seto Y, Kaminishi M, Calin GA, Croce CM. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol 2010; 11: 136-146 [PMID: 20022810 DOI: 10. 1016/S1470-2045(09)70343-2]
122. Wang XW, Wu Y, Wang D, Qin ZF. MicroRNA network analysis identifies key microRNAs and genes associated with precancerous lesions of gastric cancer. Genet Mol Res 2014; 13: 8695-8703 [PMID: 25366760 DOI: 10. 4238/2014. October. 27. 10]
123. Zhou X, Li L, Su J, Zhang G. Decreased miR-204 in H. pyloriassociated gastric cancer promotes cancer cell proliferation and invasion by targeting SOX4. PLoS One 2014; 9: e101457 [PMID: 24984017 DOI: 10. 1371/journal. pone. 0101457]
124. Song MY, Pan KF, Su HJ, Zhang L, Ma JL, Li JY, Yuasa Y, Kang D, Kim YS, You WC. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS One 2012; 7: e33608 [PMID: 22432036 DOI: 10. 1371/journal. pone. 0033608]
125. Yu X, Luo L, Wu Y, Yu X, Liu Y, Yu X, Zhao X, Zhang X, Cui L, Ye G, Le Y, Guo J. Gastric juice miR-129 as a potential biomarker for screening gastric cancer. Med Oncol 2013; 30: 365 [PMID: 23307240 DOI: 10. 1007/s12032-012-0365-y]
126. Liu WJ, Xu Q, Sun LP, Dong QG, He CY, Yuan Y. Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease. Tumour Biol 2015; 36: 3337-3343 [PMID: 25549793 DOI: 10. 1007/ s13277-014-2967-9]
127. Fu Z, Qian F, Yang X, Jiang H, Chen Y, Liu S. Circulating miR-222 in plasma and its potential diagnostic and prognostic value in gastric cancer. Med Oncol 2014; 31: 164 [PMID: 25129310 DOI: 10. 1007/ s12032-014-0164-8]
128. Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, Nakao K, Hirayama T, Kohno S. MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer 2011; 128: 361-370 [PMID: 20333682 DOI: 10. 1002/ ijc. 25348]
129. Noto JM, Peek RM. The role of microRNAs in Helicobacter pylori pathogenesis and gastric carcinogenesis. Front Cell Infect Microbiol 2011; 1: 21 [PMID: 22919587 DOI: 10. 3389/fcimb. 2011. 00021]
130. Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene 2013; 532: 1-12 [PMID: 23246696 DOI: 10. 1016/ j. gene. 2012. 12. 009]
131. Thompson RC, Vardinogiannis I, Gilmore TD. Identification of an NF-?B p50/p65-responsive site in the human MIR155HG promoter. BMC Mol Biol 2013; 14: 24 [PMID: 24059932 DOI: 10. 1186/1471-2199-14-24]
132. Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, Shi Y, Wang F, Wu Y, Tong WD, Guo H, Mao XH, Zou QM. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis 2009; 200: 916-925 [PMID: 19650740 DOI: 10. 1086/605443]
133. Saito Y, Suzuki H, Tsugawa H, Imaeda H, Matsuzaki J, Hirata K, Hosoe N, Nakamura M, Mukai M, Saito H, Hibi T. Overexpression of miR-142-5p and miR-155 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma resistant to Helicobacter pylori eradication. PLoS One 2012; 7: e47396 [PMID: 23209550 DOI: 10. 1371/journal. pone. 0047396]
134. Tang B, Xiao B, Liu Z, Li N, Zhu ED, Li BS, Xie QH, Zhuang Y, Zou QM, Mao XH. Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pyloriinduced inflammation. FEBS Lett 2010; 584: 1481-1486 [PMID: 20219467 DOI: 10. 1016/j. febslet. 2010. 02. 063]
135. Koch M, Mollenkopf HJ, Klemm U, Meyer TF. Induction of microRNA-155 is TLR-and type IV secretion system-dependent in macrophages and inhibits DNA-damage induced apoptosis. Proc Natl Acad Sci USA 2012; 109: E1153-E1162 [PMID: 22509021 DOI: 10. 1073/pnas. 1116125109]
136. Deng H, Guo Y, Song H, Xiao B, Sun W, Liu Z, Yu X, Xia T, Cui L, Guo J. MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer. Gene 2013; 518: 351-359 [PMID: 23333942 DOI: 10. 1016/j. gene. 2012. 12. 103]
137. Jia H, Zhang Z, Zou D, Wang B, Yan Y, Luo M, Dong L, Yin H, Gong B, Li Z, Wang F, Song W, Liu C, Ma Y, Zhang J, Zhao H, Li J, Yu J. MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells. PLoS One 2014; 9: e88057 [PMID: 24498243 DOI: 10. 1371/journal. pone. 0088057]
138. Lei H, Zou D, Li Z, Luo M, Dong L, Wang B, Yin H, Ma Y, Liu C, Wang F, Zhang J, Yu J, Li Y. MicroRNA-219-2-3p functions as a tumor suppressor in gastric cancer and is regulated by DNA methylation. PLoS One 2013; 8: e60369 [PMID: 23637748 DOI: 10. 1371/journal. pone. 0060369]
139. Guo LH, Li H, Wang F, Yu J, He JS. The Tumor Suppressor Roles of miR-433 and miR-127 in Gastric Cancer. Int J Mol Sci 2013; 14: 14171-14184 [PMID: 23880861 DOI: 10. 3390/ijms140714171]
140. Li P, Chen X, Su L, Li C, Zhi Q, Yu B, Sheng H, Wang J, Feng R, Cai Q, Li J, Yu Y, Yan M, Liu B, Zhu Z. Epigenetic silencing of miR-338-3p contributes to tumorigenicity in gastric cancer by targeting SSX2IP. PLoS One 2013; 8: e66782 [PMID: 23826132 DOI: 10. 1371/journal. pone. 0066782]
141. Sakamoto N, Naito Y, Oue N, Sentani K, Uraoka N, Zarni Oo H, Yanagihara K, Aoyagi K, Sasaki H, Yasui W. MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis. Cancer Sci 2014; 105: 236-243 [PMID: 24283384 DOI: 10. 1111/cas. 12330]
142. Hashimoto Y, Akiyama Y, Yuasa Y. Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer. PLoS One 2013; 8: e62589 [PMID: 23667495 DOI: 10. 1371/journal. pone. 0062589]
143. Li Z, Lei H, Luo M, Wang Y, Dong L, Ma Y, Liu C, Song W, Wang F, Zhang J, Shen J, Yu J. DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer. Gastric Cancer 2015; 18: 43-54 [PMID: 24481854 DOI: 10. 1007/s10120-014-0340-8]
144. Kiga K, Mimuro H, Suzuki M, Shinozaki-Ushiku A, Kobayashi T, Sanada T, Kim M, Ogawa M, Iwasaki YW, Kayo H, Fukuda-Yuzawa Y, Yashiro M, Fukayama M, Fukao T, Sasakawa C. Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection. Nat Commun 2014; 5: 4497 [PMID: 25187177 DOI: 10. 1038/ncomms5497]
145. Chan YC, Banerjee J, Choi SY, Sen CK. miR-210: the master hypoxamir. Microcirculation 2012; 19: 215-223 [PMID: 22171547 DOI: 10. 1111/j. 1549-8719. 2011. 00154. x]
146. Corvalán AH, Torres VA. RPRM (reprimo, TP53 dependent G2 arrest mediator candidate). Atlas Genet Cytogenet Oncol Haematol 2012; 16: 223-224
147. Ohki R, Nemoto J, Murasawa H, Oda E, Inazawa J, Tanaka N, Taniguchi T. Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase. J Biol Chem 2000; 275: 22627-22630 [PMID: 10930422 DOI: 10. 1074/jbc. C000235200]
148. Saavedra K, Valbuena J, Olivares W, Marchant MJ, Rodríguez A, Torres-Estay V, Carrasco-Avino G, Guzmán L, Aguayo F, Roa JC, Corvalán AH. Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates with Invasive Stage of Tumor Progression and p73 Expression in Gastric Cancer. PLoS One 2015; 10: e0125834 [PMID: 25954972 DOI: 10. 1371/journal. pone. 0125834]
149. Schneider BG, Peng DF, Camargo MC, Piazuelo MB, Sicinschi LA, Mera R, Romero-Gallo J, Delgado AG, Bravo LE, Wilson KT, Peek RM, Correa P, El-Rifai W. Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. Int J Cancer 2010; 127: 2588-2597 [PMID: 20178103 DOI: 10. 1002/ijc. 25274]
150. Bernal C, Aguayo F, Villarroel C, Vargas M, Díaz I, Ossandon FJ, Santibáñez E, Palma M, Aravena E, Barrientos C, Corvalan AH. Reprimo as a potential biomarker for early detection in gastric cancer. Clin Cancer Res 2008; 14: 6264-6269 [PMID: 18829507 DOI: 10. 1158/1078-0432. CCR-07-4522]
151. Hanigan MH. gamma-Glutamyl transpeptidase, a glutathionase: its expression and function in carcinogenesis. Chem Biol Interact 1998; 111-112: 333-342 [PMID: 9679564]
152. Chevalier C, Thiberge JM, Ferrero RL, Labigne A. Essential role of Helicobacter pylori gamma-glutamyltranspeptidase for the colonization of the gastric mucosa of mice. Mol Microbiol 1999; 31: 1359-1372 [PMID: 10200957]
153. Kim KM, Lee SG, Park MG, Song JY, Kang HL, Lee WK, Cho MJ, Rhee KH, Youn HS, Baik SC. Gamma-glutamyltranspeptidase of Helicobacter pylori induces mitochondria-mediated apoptosis in AGS cells. Biochem Biophys Res Commun 2007; 355: 562-567 [PMID: 17307146 DOI: 10. 1016/j. bbrc. 2007. 02. 021]
154. Kim KM, Lee SG, Kim JM, Kim DS, Song JY, Kang HL, Lee WK, Cho MJ, Rhee KH, Youn HS, Baik SC. Helicobacter pylori gammaglutamyltranspeptidase induces cell cycle arrest at the G1-S phase transition. J Microbiol 2010; 48: 372-377 [PMID: 20571956 DOI: 10. 1007/s12275-010-9293-8]
155. Gong M, Ling SS, Lui SY, Yeoh KG, Ho B. Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology 2010; 139: 564-573 [PMID: 20347814 DOI: 10. 1053/j. gastro. 2010. 03. 050]
156. Ricci V, Giannouli M, Romano M, Zarrilli R. Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role. World J Gastroenterol 2014; 20: 630-638 [PMID: 24574736 DOI: 10. 3748/ wjg. v20. i3. 630]
157. Lladser A, Sanhueza C, Kiessling R, Quest AF. Is survivin the potential Achilles' heel of cancer? Adv Cancer Res 2011; 111: 1-37 [PMID: 21704829 DOI: 10. 1016/B978-0-12-385524-4. 00001-5]
158. Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC. IAP regulation of metastasis. Cancer Cell 2010; 17: 53-64 [PMID: 20129247 DOI: 10. 1016/j. ccr. 2009. 11. 021]
159. Fernández JG, Rodríguez DA, Valenzuela M, Calderon C, Urzúa U, Munroe D, Rosas C, Lemus D, Díaz N, Wright MC, Leyton L, Tapia JC, Quest AF. Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced ?-catenin/Tcf-Lef dependent transcription. Mol Cancer 2014; 13: 209 [PMID: 25204429 DOI: 10. 1186/1476-4598-13-209]
160. Valenzuela M, Pérez-Pérez G, Corvalán AH, Carrasco G, Urra H, Bravo D, Toledo H, Quest AF. Helicobacter pylori-induced loss of the inhibitor-of-apoptosis protein survivin is linked to gastritis and death of human gastric cells. J Infect Dis 2010; 202: 1021-1030 [PMID: 20735270 DOI: 10. 1086/656143]
161. Valenzuela M, Bravo D, Canales J, Sanhueza C, Díaz N, Almarza O, Toledo H, Quest AF. Helicobacter pylori-induced loss of survivin and gastric cell viability is attributable to secreted bacterial gammaglutamyl transpeptidase activity. J Infect Dis 2013; 208: 1131-1141 [PMID: 23847060 DOI: 10. 1093/infdis/jit286]
162. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science 2004; 306: 1568-1571 [PMID: 15567866 DOI: 10. 1126/science. 1099513]