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Gut Liver. 2020;14(5):571-580.

Helicobacter pylori Eradication Can Reverse the Methylation-Associated Regulation of miR-200a/b in Gastric Carcinogenesis.

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제1저자 최지민 · 교신저자 김상균

소속 (5)
  1. Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
  2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  3. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
  4. Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  5. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

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.

Keywords

Epigenetic alterationHelicobacter pyloriMethylationMicroRNAsStomach neoplasm

Figures

Fig. 1
Fig. 1 Changes in promoter DNA methylation and microRNA (miRNA) expression following demethylating treatment in gastric cancer (GC) cell lines. (A) Promoter DNA methylation levels. The methylation levels of the promoter region of miR-200a and miR-200b was decreased in three GC cell lines after 72 hours of treatment with the demethylating agent 5-Aza-2’-deoxycytidine. (B) Relative expression levels. After 72 hours of treatment with the demethylating agent, the expression levels of both miR-200a and miR-200b increased in three GC cell lines. PMR, percentage of methylated reference.
Fig. 2
Fig. 2 The levels of promoter DNA methylation and corresponding miRNA expression in the study groups. The levels of miR-200a/b methylation are presented as medians and interquartile ranges. The levels of miR-200a/b expression are shown as fold changes relative to the Helicobacter pylori-negative controls and standard deviations. (A) miR-200a. The promoter levels of miR-200a (left) methylation were lowest in the H. pylori-negative controls, followed by the H. pylori-positive controls and then the H. pylori-positive GCs (all p<0.001). The miR-200a expression (right) level was highest in the H. pylori-negative controls, followed by the H. pylori-positive controls and then the H. pylori-positive GCs (all p<0.001). (B) miR-200b. miR-200b showed the same pattern as miR-200a for promoter DNA methylation and expression. miRNA, microRNA; PMR, percentage of methylated reference; GC, gastric cancer. *p<0.001.
Fig. 3
Fig. 3 Change in promoter DNA methylation and corresponding microRNA (miRNA) expression according to the Helicobacter pylori eradication therapy. (A) miR-200a and (B) miR-200b. In the H. pylori-eradication group, there was a significant difference in the promoter methylation and expression levels of miR-200a/b at 6 months after eradication. FU, follow-up.

그림 출처: PubMed Central 공개 논문 (PMC7492500)

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Conflict of interest statement

CONFLICTS OF INTEREST. No potential conflict of interest relevant to this article was reported.

그 밖의 정보
출판 형태
Journal Article
저널
Gut and liver · eISSN 2005-1212
MeSH
Aged · Carcinogenesis / metabolism · Female · Gastric Mucosa / metabolism · Helicobacter Infections* / metabolism · Helicobacter pylori* / metabolism · Humans · Male · Methylation · MicroRNAs / genetics · Middle Aged · Stomach Neoplasms* / metabolism
Substances
MIRN200 microRNA, human · MicroRNAs
참고문헌
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