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

Gut and Liver 2020년 14권 5호 p.571 ~ 580
최지민, 김상균, 양효준, 임주현, 조남윤, 김우호, 김주성, 정현채,
소속 상세정보
최지민 ( Choi Ji-Min ) - Seoul National University Hospital Healthcare System Gangnam Center Department of Internal Medicine
김상균 ( Kim Sang-Gyun ) - Seoul National University College of Medicine Department of Internal Medicine
양효준 ( Yang Hyo-Joon ) - Sungkyunkwan University School of Medicine Kangbuk Samsung Hospital Department of Internal Medicine
임주현 ( Lim Joo-Hyun ) - Seoul National University Hospital Healthcare System Gangnam Center Department of Internal Medicine
조남윤 ( Cho Nam-Yun ) - Seoul National University College of Medicine Cancer Research Institute Laboratory of Epigenetics
김우호 ( Kim Woo-Ho ) - Seoul National University College of Medicine Department of Pathology
김주성 ( Kim Joo-Sung ) - Seoul National University Hospital Healthcare System Gangnam Center Department of Internal Medicine
정현채 ( Jung Hyun-Chae ) - Seoul National University College of Medicine Department of Internal Medicine

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.

키워드

Helicobacter pylori; MicroRNAs; Methylation; Epigenetic alteration; Stomach neoplasm

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