CagA mediates epigenetic regulation to attenuate let-7 expression in<i>Helicobacter pylori</i>-related carcinogenesis

Hayashi, Yoshito; Tsujii, Masahiko; Wang, Jun; Kondo, Jumpei; Akasaka, Tomofumi; Jin, Ying; Li, Wei; Nakamura, Tôru; Nishida, Tsutomu; Iijima, Hideki; Tsuji, S.; Kawano, Seiji; Hayashi, Norio; Takehara, Tetsuo

doi:10.1136/gutjnl-2011-301625

Cited by 116 publications

(89 citation statements)

References 48 publications

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“…MiRNAs were found to be dysregulated in several human cancers including GC [16,17,18]. Han reported that miR-29c acts as a tumor suppressor in GC by directly targeting ITGB1 [16].…”

Section: Discussionmentioning

confidence: 99%

The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer

Zhou

Feng

Yin

et al. 2015

Cell Physiol Biochem

198

148

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Background/Aims: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been demonstrated to promote malignancy in various cancers. We aimed to determine the correlation between miR-141 and H19 and their roles in gastric cancer in this study. Methods: H19 and miR-141 expression were detected by qRT-PCR. By bioinformatic analysis and luciferase assay we examined the correlation between H19 and miR-141 in vitro. Results: H19 expression was found to be inversely correlated to miR-141 expression in gastric cancer cells and tissues. H19 promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in human cancer cells. MiR-141 binds to H19 in a sequence specific manner, and suppresses H19 expression and functions including proliferation and invasion. MiR-141 could also regulate H19 target genes and miR-141 inhibitor restores H19 siRNA function, while H19 regulates miR-141 target gene ZEB1. Conclusion: These results were the first to demonstrate that H19 and miR-141 could compete with each other and affect their target genes in gastric cancer, which provide important clues for understanding the key roles of lncRNA-miRNA functional network in cancer.

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“…MiRNAs were found to be dysregulated in several human cancers including GC [16,17,18]. Han reported that miR-29c acts as a tumor suppressor in GC by directly targeting ITGB1 [16].…”

Section: Discussionmentioning

confidence: 99%

The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer

Zhou

Feng

Yin

et al. 2015

Cell Physiol Biochem

198

148

View full text Add to dashboard Cite

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“…Tumor-associated miR-7 and miR-146a are deregulated by inflammation factors that are produced through the interaction between CagA and the host cell ( fig. 1) [2][3][4][5][6].Epigenetic regulation of miRNAs is also important for deregulation of miRNAs in gastric cancer. DNA hypomethylation and promoter methylation change the miRNA expression profile; the former causes miR-196b overexpression and the latter results in down-regulation of miR-124a [7][8].…”

mentioning

confidence: 99%

“…Tumor-associated miR-7 and miR-146a are deregulated by inflammation factors that are produced through the interaction between CagA and the host cell ( fig. 1) [2][3][4][5][6].…”

mentioning

confidence: 99%

Mechanisms of MicroRNA Deregulation and MicroRNA Targets in Gastric Cancer

Irmak-Yazicioglu

2016

Oncol Res Treat

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Reduced or increased levels of mature microRNAs (miRNAs) in tumors are often the result of deregulated transcription, epigenetic silencing, genetic loss, or defects in their biogenesis pathway in gastric cancer. Among these, Helicobacter pylori infection, epigenetic regulation and defects in the pathway of miRNA biogenesis predominate in gastric cancer [1].The miRNA profile seen in gastric cancer tissues, when compared to that of healthy controls, reveals several reasons for this. H. pylori is an etiological factor for gastric carcinogenesis. Upon infection with H. pylori, miR-21 is up-regulated while miR-218 is down-regulated in gastric epithelial tissues and AGS cells. CagA is a virulence factor of this bacteria and prevents expression of Let-7 by promoting methylation of its promoter. Tumor-associated miR-7 and miR-146a are deregulated by inflammation factors that are produced through the interaction between CagA and the host cell ( fig. 1) [2][3][4][5][6].Epigenetic regulation of miRNAs is also important for deregulation of miRNAs in gastric cancer. DNA hypomethylation and promoter methylation change the miRNA expression profile; the former causes miR-196b overexpression and the latter results in down-regulation of miR-124a [7][8]. The miR-17-92 cluster is located at a fragile site in the genome [9], and has been found to be overexpressed in many cancers including gastric cancer [10]. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer [11]. E2F1 overexpression is a biomarker for gastric cancer and E2F1 transcriptionally targets and up-regulates the miR-106b/25 cluster, and up-regulated miR-106b/25 and miR-93 repress E2F1 transcription within a negative feedback loop in gastric cancer cells ( fig. 2) [12].

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“…In addition, novel risk markers of gastric cancer were identified by the microarray analysis for hypermethylated CpG islands [129]. A recent study revealed that CagA of H. pylori causes aberrant epigenetic silencing of let-7 followed by upregulation of Ras oncoprotein using in vitro experiments and an in vivo mouse model [130].…”

Section: Epigeneticsmentioning

confidence: 99%

Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

et al. 2014

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Since the discovery of Helicobacter pylori (H. pylori), many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful for the analysis of H. pylori-associated inflammatory reactions and gastric cancer development. Inhibitors of oxidative stress, cyclooxygenase-2 (COX-2) and nuclear factor-κB, exert preventive effects on chronic gastritis and the development of adenocarcinomas in H. pylori-infected gerbils. Genetically-modified mouse models, including transgenic and knockout mice, have also revealed the importance of p53, COX-2/prostaglandin, Wnt/β-catenin, proinflammatory cytokines, gastrin and type III mucin in the molecular mechanisms of gastric carcinogenesis. Microarray technology is available for comprehensive gene analysis in the gastric mucosa of mouse models, and epigenetics, such as DNA methylation, could be an alternative approach to correlate the observations in animal models with the etiology in humans.

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CagA mediates epigenetic regulation to attenuate let-7 expression inHelicobacter pylori-related carcinogenesis

Abstract: H pylori CagA induces aberrant epigenetic silencing of let-7 expression, leading to Ras upregulation.

Cited by 116 publications

References 48 publications

The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer

The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer

Mechanisms of MicroRNA Deregulation and MicroRNA Targets in Gastric Cancer

Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

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