Helicobacter pylori Eradication Can Reverse the Methylation-Associated Regulation of miR-200a/b in Gastric Carcinogenesis
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Background/Aims: Epigenetic change is one of the mechanisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigenetic changes of miR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. Methods: The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mucosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori -eradication and H. pylori -persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the methylation levels. Results: In the GC cell lines, the level of miR- 200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order. In the H. pylori -persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methylation decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. Conclusions: Epigenetic alterations of miR-200a/b may be implicated in H. pylori -induced gastric carcinogenesis. This field defect for cancerization is suggested to be improved by H. pylori eradication.
Abstract
Background/Aims: Epigenetic change is one of the mechanisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigenetic changes of miR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. Methods: The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mucosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori -eradication and H. pylori -persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the methylation levels. Results: In the GC cell lines, the level of miR- 200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order. In the H. pylori -persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methylation decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. Conclusions: Epigenetic alterations of miR-200a/b may be implicated in H. pylori -induced gastric carcinogenesis. This field defect for cancerization is suggested to be improved by H. pylori eradication.
참고문헌 (39)
- Ferlay J, "Cancer incidence and mortality worldwide : sources, methods and major patterns in GLOBOCAN 2012", Int J Cancer, 136, pp.E359~E386 (2015)
- Aesun Shin, "Gastric Cancer Epidemiology in Korea", Journal of Gastric Cancer, 11(3), pp.135~140 (2011), 대한위암학회
- Correa P, "Human gastric carcinogenesis : a multistep and multifactorial process : First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention", Cancer Res, 52, pp.6735~6740 (1992)
- Ushijima T, "Focus on gastric cancer", Cancer Cell, 5, pp.121~125 (2004)
- Maekita T, "High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk", Clin Cancer Res, 12(3 Pt 1), pp.989~995 (2006)
- D’Angelo E, "MicroRNAs as tools and effectors for patient treatment in gastrointestinal carcinogenesis", Curr Drug Targets, 16, pp.383~392 (2015)
- Ramachandran K, "DNA methylation and field cancerization", Epigenomics, 4, pp.243~245 (2012)
- Ando T, "DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients : its possible involvement in the formation of epigenetic field defect", Int J Cancer, 124, pp.2367~2374 (2009)
- Hayes J, "MicroRNAs in cancer : biomarkers, functions and therapy", Trends Mol Med, 20, pp.460~469 (2014)
- Chen WS, "Silencing of miR-1-1 and miR-133a-2 cluster expression by DNA hypermethylation in colorectal cancer", Oncol Rep, 28, pp.1069~1076 (2012)
- Tsai KW, "Aberrant hypermethylation of miR-9 genes in gastric cancer", Epigenetics, 6, pp.1189~1197 (2011)
- Peng S, "Association of microRNA-196a-2 gene polymorphism with gastric cancer risk in a Chinese population", Dig Dis Sci, 55, pp.2288~2293 (2010)
- Tsai KW, "Epigenetic regulation of miR-196b expression in gastric cancer", Genes Chromosomes Cancer, 49, pp.969~980 (2010)
- Bojmar L, "The role of microRNA-200in progression of human colorectal and breast cancer", PLoS One, 8, pp.e84815~ (2013)
- Song F, "Integrated microRNA network analyses identify a poor-prognosis subtype of gastric cancer characterized by the miR-200 family", Clin Cancer Res, 20, pp.878~889 (2014)
- Kurashige J, "MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma", Ann Surg Oncol, 19(Suppl 3), pp.S656~S664 (2012)
- Wiklund ED, "Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer", Int J Cancer, 128, pp.1327~1334 (2011)
- Duns G, "The entire miR-200seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney", Genes Chromosomes Cancer, 52, pp.165~173 (2013)
- Liu XG, "High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer", Med Oncol, 29, pp.618~626 (2012)
- Cristóbal I, "Deregulation of miR-200b, miR-200c and miR-429 indicates its potential relevant role in patients with colorectal cancer liver metastasis", J Surg Oncol, 110, pp.484~485 (2014)
- Bendoraite A, "Regulation of miR-200family microRNAs and ZEB transcription factors in ovarian cancer : evidence supporting a mesothelial-to-epithelial transition", Gynecol Oncol, 116, pp.117~125 (2010)
- Chang L, "Expression and clinical significance of the microRNA-200 family in gastric cancer", Oncol Lett, 9, pp.2317~2324 (2015)
- Zhou X, "The downregulation of miR-200c", 141 promotes ZEB1, Med Oncol, pp.2015, 32[DOI]
- Batista L, "Regulation of miR-200c", 141 expression by intergenic DNA-looping and transcriptional read-through, 2016, pp.7, 8959~
- Dixon MF, "Classification and grading of gastritis : the updated Sydney System : International Workshop on the Histopathology of Gastritis, Houston 1994", Am J Surg Pathol, 20, pp.1161~1181 (1996)
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))method", Methods, 25, pp.402~408 (2001)
- Trinh BN, "DNA methylation analysis by MethyLight technology", Methods, 25, pp.456~462 (2001)
- Eads CA, "MethyLight : a highthroughput assay to measure DNA methylation", Nucleic Acids Res, 28, pp.E32~ (2000)
- Toshikazu Ushijima, "Epigenetic Field for Cancerization", BMB reports, 40(2), pp.142~150 (2007), 한국생화학분자생물학회
- Joo Hyun Lim, "Helicobacter pylori Is Associated with miR-133a Expression through Promoter Methylation in Gastric Carcinogenesis", Gut and Liver, 12(1), pp.58~66 (2018), 거트앤리버 소화기연관학회협의회
- Isomoto H, "Endoscopic submucosal dissection for early gastric cancer : a large-scale feasibility study", Gut, 58, pp.331~336 (2009)
- Yang Q, "Dysregulation of non-coding RNAs in gastric cancer", World J Gastroenterol, 21, pp.10956~10981 (2015)
- Pan HW, "MicroRNA dysregulation in gastric cancer", Curr Pharm Des, 19, pp.1273~1284 (2013)
- Davalos V, "Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis", Oncogene, 31, pp.2062~2074 (2012)
- Enkhbaatar Z, "KDM5B histone demethylase controls epithelial-mesenchymal transition of cancer cells by regulating the expression of the microRNA-200 family", Cell Cycle, 12, pp.2100~2112 (2013)
- Choi JM, "Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention : a randomized controlled trial", Gastrointest Endosc, 88, pp.475~485 (2018)
- Tsuda M, "Effect on Helicobacter pylori eradication therapy against gastric cancer in Japan", Helicobacter, 22, pp.e12415~ (2017)
- Wang F, "Helicobacter pylori-induced gastric inflammation and gastric cancer", Cancer Lett, 345, pp.196~202 (2014)
- Lamb A, "Role of the Helicobacter pylori-induced inflammatory response in the development of gastric cancer", J Cell Biochem, 114, pp.491~497 (2013)