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Journal of Gastroenterology
Published in: Journal of Gastroenterology 9/2012

01-09-2012 | Original Article—Alimentary Tract

H. pylori eradication did not improve dysregulation of specific oncogenic miRNAs in intestinal metaplastic glands

Authors: Akiko Shiotani, Noriya Uedo, Hiroyasu Iishi, Takahisa Murao, Tomoko Kanzaki, Yoshiki Kimura, Tomoari Kamada, Hiroaki Kusunoki, Kazuhiko Inoue, Ken Haruma

Published in: Journal of Gastroenterology | Issue 9/2012

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Abstract

Background

Many microRNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue.

Aim

We aimed to compare the effect of H. pylori eradication on gastric mucosal miRNAs in subjects in a high-risk group for gastric cancer compared to controls.

Methods

Patients with a recent history of endoscopic resection for early gastric cancer and sex- and age-matched non-cancer controls were enrolled. The expression of 21 miRNAs was examined using gastric mucosal biopsy specimens and microdissected gastric glands from the lesser and greater curvatures of the gastric corpus both before and one year after H. pylori eradication.

Results

Twenty patients and 14 controls were enrolled. The expression of oncogenic miRNAs (miR-17/92 and the miR-106b-93-25 cluster, miR-21, miR-194, and miR-196) was significantly higher in the gastric mucosa of the cancer group than in the controls. H. pylori eradication resulted in a significant fall in the expression of oncogenic miRNAs only in the controls, whereas miR-223 expression was decreased and let-7d expression was increased in both groups. miR-196 was expressed only in intestinal metaplastic glands. The expression of oncogenic miRNAs was significantly higher in the intestinal metaplastic glands than in the non-intestinal metaplastic glands irrespective of H. pylori eradication. In neither group did H. pylori eradication significantly change any miRNA expression in the intestinal metaplastic glands.

Conclusion

Dysregulation of specific miRNAs is present in H. pylori-induced corpus gastritis. H. pylori eradication improved miRNA dysregulation, but not in intestinal metaplastic glands or in the gastric mucosa of patients in a high-risk group for gastric cancer.
Literature
1.
Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000;404:293–6.PubMedCrossRef
2.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.PubMedCrossRef
3.
Wu WK, Lee CW, Cho CH, Fan D, Wu K, Yu J, et al. MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene. 2010;29:5761–71.
4.
5.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.PubMedCrossRef
6.
Wang J, Wang Q, Liu H, Hu B, Zhou W, Cheng Y. MicroRNA expression and its implication for the diagnosis and therapeutic strategies of gastric cancer. Cancer Lett. 2010;297:137–43.PubMedCrossRef
7.
Belair C, Darfeuille F, Staedel C. Helicobacter pylori and gastric cancer: possible role of microRNAs in this intimate relationship. Clin Microbiol Infect. 2009;15:806–12.PubMedCrossRef
8.
Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.PubMedCrossRef
9.
Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, et al. Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 2009;37:1672–81.PubMedCrossRef
10.
Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008;133:217–22.PubMedCrossRef
11.
Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.PubMedCrossRef
12.
Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA. 2008;105:7004–9.PubMedCrossRef
13.
Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007;282:14328–36.PubMedCrossRef
14.
Bueno MJ, Perez de Castro I, Gomez de Cedron M, Santos J, Calin GA, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13:496–506.PubMedCrossRef
15.
Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2010;31:766–76.PubMedCrossRef
16.
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120:635–47.PubMedCrossRef
17.
Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007;315:1576–9.PubMedCrossRef
18.
Sampson VB, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, et al. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 2007;67:9762–70.PubMedCrossRef
19.
Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9:582–9.PubMedCrossRef
20.
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601.PubMedCrossRef
21.
Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22:894–907.PubMedCrossRef
22.
Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, et al. MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011;128:361–70.PubMedCrossRef
23.
Shiotani A, Murao T, Uedo N, Iishi H, Yamanaka Y, Kamada T, et al. Eradication of H. pylori did not improve abnormal Sonic Hedgehog expression in the high risk group for gastric cancer. Dig Dis Sci. 2012;57:643–9.PubMedCrossRef
24.
Baldini L, Pretolani S, Bonvicini F, Miglio F, Epifanio G, Gentiloni Silveri N, et al. Effect of Helicobacter pylori infection, age and epithelial cell turnover in a general population at high risk for gastric cancer. Panminerva Med. 1999;41:187–92.PubMed
25.
Lynch DA, Mapstone NP, Clarke AM, Jackson P, Moayyedi P, Dixon MF, et al. Correlation between epithelial cell proliferation and histological grading in gastric mucosa. J Clin Pathol. 1999;52:367–71.PubMedCrossRef
26.
Sougioultzis S, Foukas PG, Tzivras M, Kourtessas D, Gorgoulis VG, Davaris P, et al. Alterations in the proliferating compartment of gastric mucosa during Helicobacter pylori infection: the putative role of epithelial cells expressing p27(kip1). Mod Pathol. 2003;16:1076–85.PubMedCrossRef
27.
Shiotani A, Iishi H, Ishiguro S, Tatsuta M, Nakae Y, Merchant JL. Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions. J Gastroenterol. 2005;40:337–44.PubMedCrossRef
28.
Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, et al. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood. 2009;113:3314–22.PubMedCrossRef
29.
Chen C, Zhang Y, Zhang L, Weakley SM, Yao Q. MicroRNA-196: critical roles and clinical applications in development and cancer. J Cell Mol Med. 2011;15:14–23.PubMedCrossRef
30.
Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005;438:671–4.PubMedCrossRef
31.
Hammerschmidt M, Brook A, McMahon AP. The world according to hedgehog. Trends Genet. 1997;13:14–21.PubMedCrossRef
32.
Bitgood MJ, McMahon AP. Hedgehog and Bmp genes are coexpressed at many diverse sites of cell–cell interaction in the mouse embryo. Dev Biol. 1995;172:126–38.PubMedCrossRef
33.
Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993;75:1417–30.PubMedCrossRef
34.
Shiotani A, Nishi R, Uedo N, Iishi H, Tsutsui H, Ishii M, et al. Helicobacter pylori eradication prevents extension of intestinalization even in the high-risk group for gastric cancer. Digestion. 2010;81:223–30.PubMedCrossRef
35.
Shiotani A, Uedo N, Iishi H, Tatsuta M, Ishiguro S, Nakae Y, et al. Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia. Int J Cancer. 2007;121:1182–9.PubMedCrossRef
36.
Wong QW, Lung RW, Law PT, Lai PB, Chan KY, To KF, Wong N. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 2008;135:257–69.PubMedCrossRef
37.
Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest. 2008;88:1358–66.PubMedCrossRef
38.
Xiao B, Guo J, Miao Y, Jiang Z, Huan R, Zhang Y, et al. Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta. 2009;400:97–102.PubMedCrossRef
39.
Motoyama K, Inoue H, Mimori K, Tanaka F, Kojima K, Uetake H, et al. Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer. Int J Oncol. 2010;36:1089–95.PubMed
40.
41.
Graham DY, Uemura N. Natural history of gastric cancer after Helicobacter pylori eradication in Japan: after endoscopic resection, after treatment of the general population, and naturally. Helicobacter. 2006;11:139–43.PubMedCrossRef
42.
Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008;451:1125–9.PubMedCrossRef
43.
Fukao T, Fukuda Y, Kiga K, Sharif J, Hino K, Enomoto Y, et al. An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell. 2007;129:617–31.PubMedCrossRef
44.
45.
Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 2009;8:843–52.PubMedCrossRef
46.
Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130–5.PubMedCrossRef
47.
Nakada C, Matsuura K, Tsukamoto Y, Tanigawa M, Yoshimoto T, Narimatsu T, et al. Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol. 2008;216:418–27.PubMedCrossRef
48.
Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67:6092–9.PubMedCrossRef
49.
Hu M, Xia M, Chen X, Lin Z, Xu Y, Ma Y, et al. MicroRNA-141 regulates Smad interacting protein 1 (SIP1) and inhibits migration and invasion of colorectal cancer cells. Dig Dis Sci. 2010;55:2365–72.PubMedCrossRef
50.
Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67:8699–707.PubMedCrossRef
51.
Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, et al. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer. 2006;5:29–38.PubMedCrossRef
52.
Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72:397–402.PubMedCrossRef
53.
Michael MZ, O’ Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003;1:882–91.PubMed
54.
Dijckmeester WA, Wijnhoven BP, Watson DI, Leong MP, Michael MZ, Mayne GC, et al. MicroRNA-143 and -205 expression in neosquamous esophageal epithelium following Argon plasma ablation of Barrett’s esophagus. J Gastrointest Surg. 2009;13:846–53.PubMedCrossRef
55.
Ng EK, Tsang WP, Ng SS, Jin HC, Yu J, Li JJ, et al. MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer. Br J Cancer. 2009;101:699–706.PubMedCrossRef
56.
Krutzfeldt J, Rosch N, Hausser J, Manoharan M, Zavolan M, Stoffel M. MicroRNA-194 is a target of transcription factor 1 (Tcf1, Hnf1alpha) in adult liver and controls expression of frizzled-6. Hepatology. 2012;55:98–107.PubMedCrossRef
57.
Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J, et al. MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer. 2011;10:99–107.PubMedCrossRef
58.
Huang J, Zhao L, Xing L, Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28:357–64.PubMed
59.
Wang FE, Zhang C, Maminishkis A, Dong L, Zhi C, Li R, et al. MicroRNA-204/211 alters epithelial physiology. FASEB J. 2010;24:1552–71.PubMedCrossRef
60.
Yang Z, Chen S, Luan X, Li Y, Liu M, Li X, et al. MicroRNA-214 is aberrantly expressed in cervical cancers and inhibits the growth of HeLa cells. IUBMB Life. 2009;61:1075–82.PubMedCrossRef
61.
Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9:824–33.PubMedCrossRef
62.
Xu Y, Deng Y, Yan X, Zhou T. Targeting miR-375 in gastric cancer. Expert Opin Ther Targets. 2011;15:961–72.PubMedCrossRef
Metadata
Title
H. pylori eradication did not improve dysregulation of specific oncogenic miRNAs in intestinal metaplastic glands
Authors
Akiko Shiotani
Noriya Uedo
Hiroyasu Iishi
Takahisa Murao
Tomoko Kanzaki
Yoshiki Kimura
Tomoari Kamada
Hiroaki Kusunoki
Kazuhiko Inoue
Ken Haruma
Publication date
01-09-2012
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 9/2012
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0562-7

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