JMJD2B is required for<i>Helicobacter pylori</i>-induced gastric carcinogenesis via regulating COX-2 expression

Han, Fengjuan; Ren, Juchao; Zhang, Jinjin; Sun, Yuan; Ma, Fengwang; Liu, Zhifang; Yu, Han; Jia, Jihui; Li, Wenjuan

doi:10.18632/oncotarget.9573

Cited by 30 publications

(38 citation statements)

References 36 publications

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“…Herein, we have shown that possible downstream targets of NFκB and STAT3 pathways including TGFβ, HGF, IL‐6, IL‐8, TNC, collagens I and III were upregulated in fibroblasts infected by H. pylori (cagA+vacA+). We have also observed a significant induction of COX‐2 mRNA expression, which is closely associated with the formation and development of majority of gastric cancers 61, 62…”

Section: Discussionmentioning

confidence: 53%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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BackgroundMajor human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori‐infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H. pylori and fibroblasts remains unknown. We determined the effect of coincubation of normal rat gastric fibroblasts with alive H. pylori (cagA+vacA+) and H. pylori (cagA−vacA−) strains on the differentiation of these fibroblasts into cells possessing characteristics of cancer‐associated fibroblasts (CAFs) able to induce epithelial‐mesenchymal transition (EMT) of normal rat gastric epithelial cells (RGM‐1).Materials and MethodsThe panel of CAFs markers mRNA was analyzed in H. pylori (cagA+vacA+)‐infected fibroblasts by RT‐PCR. After insert coculture of differentiated fibroblasts with RGM‐1 cells from 24 up to 48, 72, and 96 hours, the mRNA expression for EMT‐associated genes was analyzed by RT‐PCR.ResultsThe mRNA expression for CAFs markers was significantly increased after 72 hours of infection with H. pylori (cagA+vacA+) but not H. pylori (cagA−vacA−) strain. Following coculture with CAFs, RGM‐1 cells showed significant decrease in E‐cadherin mRNA, and the parallel increase in the expression of Twist and Snail transcription factors mRNA was observed along with the overexpression of mRNAs for TGFβR, HGFR, FGFR, N‐cadherin, vimentin, α‐SMA, VEGF, and integrin‐β1.Conclusion Helicobacter pylori (cagA+vacA+) strain induces differentiation of normal fibroblasts into CAFs, likely to initiate the EMT process in RGM‐1 epithelial cell line.

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Section: Discussionmentioning

confidence: 53%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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“…As one of the core factors of the Wnt signal pathway, β‐catenin widely exists in all kinds of cells and has multiple functions . β‐catenin mainly exists in the membrane of cells and to a lesser extent in the cytoplasm of cells.…”

Section: Discussionmentioning

confidence: 99%

The role and molecular mechanism of Trop2 induced epithelial‐mesenchymal transition through mediated β‐catenin in gastric cancer

et al. 2019

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The present study elucidates the potential role of Trop2 in tumor invasion and the promotion of epithelial‐mesenchymal transition (EMT) when binding β‐catenin in GC. The role of Trop2 in promoting EMT in GC cells was examined by a variety of experimental assays. Moreover, the underlying molecular mechanism of Trop2 in promoting EMT was studied by in vivo and in vitro assays. The Trop2 expression in relation to tumor metastasis status was detected by IHC in 248 cases of GC tissues and 86 cases of matched adjacent tissues. Trop2 promoted the metastasis and induces EMT in GC. Meanwhile, the elevated protein levels of Trop2 and mesenchymal markers were also found in the TGF‐β1‐induced EMT model in GC cells. Importantly, Trop2 physically bound and activated β‐catenin to promote EMT; moreover, Trop2 increased the accumulation of β‐catenin in the nucleus to accelerate metastasis in GC cells. Inhibition of Trop2 expression in GC cells prevented the migration and invasion of GC cells in vivo. Trop2+/vimentin+ expression was higher in GC tissues than that in matched adjacent tissues, and Trop2+/vimentin+ expression in GC was associated with the differentiation, TNM stage, and distant metastases. These sets of data reveal a novel regulatory network of Trop2 in EMT and GC metastasis, suggesting Trop2 as a useful marker for inducing EMT and metastasis of GC, which may help to lead a better understanding of the pathogenesis of the GC.

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“…KDM4B also upregulates miR‐125b expression and activates the Wnt signaling pathway . After Helicobacter pylori infection, KDM4B induced by the β‐catenin pathway along with nuclear factor‐κB (NF‐κB) binds to the cyclooxygenase‐2 (COX‐2) promoter to COX2 transcription . Expression levels of KDM4B and COX‐2 gradually increase in human gastric tissues during progression from infection‐related gastritis to gastric cancer.…”

Section: Altered Expression and Functions Of Kdm4s In Cancermentioning

confidence: 99%

“…102 After Helicobacter pylori infection, KDM4B induced by the β-catenin pathway along with nuclear factor-κB (NF-κB) binds to the cyclooxygenase-2 (COX-2) promoter to COX2 transcription. 103 Expression levels of KDM4B and COX-2 gradually increase in human gastric tissues during progression from infection-related gastritis to gastric cancer. Furthermore, KDM4B expression is positively correlated with COX-2 expression in both gastritis and gastric cancer tissues.…”

Section: Gastric Cancermentioning

confidence: 99%

Advances in histone demethylase KDM4 as cancer therapeutic targets

et al. 2020

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The KDM4 subfamily H3K9 histone demethylases are epigenetic regulators that control chromatin structure and gene expression by demethylating histone H3K9, H3K36, and H1.4K26. The KDM4 subfamily mainly consists of four proteins (KDM4A‐D), all harboring the Jumonji C domain (JmjC) but with differential substrate specificities. KDM4A‐C proteins also possess the double PHD and Tudor domains, whereas KDM4D lacks these domains. KDM4 proteins are overexpressed or deregulated in multiple cancers, cardiovascular diseases, and mental retardation and are thus potential therapeutic targets. Despite extensive efforts, however, there are very few KDM4‐selective inhibitors. Defining the exact physiological and oncogenic functions of KDM4 demethylase will provide the foundation for the discovery of novel potent inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM4s and the interplay between KDM4‐mediated epigenetic and metabolic pathways in cancer. We also review currently available KDM4 inhibitors and discuss their potential as therapeutic agents for cancer treatment.

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JMJD2B is required forHelicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression

Cited by 30 publications

References 36 publications

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

The role and molecular mechanism of Trop2 induced epithelial‐mesenchymal transition through mediated β‐catenin in gastric cancer

Advances in histone demethylase KDM4 as cancer therapeutic targets

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