<i>Helicobacter pylori CagA</i> promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

Ou, Yvonne; Ren, Haifeng; Zhao, Rongrong; Song, Lê Hữu; Liu, Zhengxia; Xu, Wenting; Liu, Yakun; Wang, Siying

doi:10.1002/mc.23025

Cited by 33 publications

(37 citation statements)

References 46 publications

(49 reference statements)

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“…Qu Y et al showed that miR-155 downregulated the expression of TGFβR2 to promote the proliferation and migration of GC cells, which is consistent with our study [40]. Moreover, it was reported that Helicobacter pylori infection was closely linked to miR-155, possibly upregulating miR-155 expression to inhibit the DNA mismatch repair (MMR) gene and induce a mutant phenotype that is conducive to error-prone translation synthesis and thus promotes GC progression [41][42][43]. However, some studies have reported that miR-155 is expressed at low levels in GC tissue and acts as a tumor suppressor gene [44][45][46].…”

Section: Discussionsupporting

confidence: 90%

Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer

Tian

Tan

et al. 2020

Mol Cancer

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Background: We previously reported an inverse relationship between B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP), which is associated with the prognosis of gastric cancer (GC). In this study, we further explored the microRNA (miRNA) regulatory mechanism between Bmi-1 and RKIP. Methods: Microarray analysis was first carried out to identify miRNA profiles that were differentially expressed in cells overexpressing Bmi-1. Then, miRNAs that could regulate RKIP were identified. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of Bmi-1, miR-155, miR-27a and RKIP. RKIP was confirmed as a target of miR-27a and miR-155 through luciferase reporter assays, qRT-PCR and Western blotting. The effects of the Bmi-1/miR-27a/RKIP and Bmi-1/miR-155/RKIP axes on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo. Results: The downregulation of RKIP by Bmi-1 occurred at the protein but not mRNA level. This indicates probable posttranscriptional regulation. miRNA expression profiles of cells with ectopic expression of Bmi-1 were analyzed and compared to those of control cells by microarray analysis. A total of 51 upregulated and 72 downregulated miRNAs were identified. Based on publicly available algorithms, miR-27a and miR-155 were predicted, selected and demonstrated to target RKIP. Bmi-1, miR-27a and miR-155 are elevated in human GC and associated with poor prognosis of GC, while RKIP is expressed at lower levels in GC and correlated with good prognosis. Then, in vitro tests shown that in addition to regulating RKIP expression via miR-27a and miR-155, Bmi-1 was also able to regulate the migration, invasion, proliferation, colony-formation ability and chemosensitivity of GC cells through the same pathway. Finally, the in vivo test showed similar results, whereby the knockdown of the Bmi-1 gene led to the inhibition of tumor growth, metastasis and chemoresistance through miR-27a and miR-155.

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Section: Discussionsupporting

confidence: 90%

Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer

Tian

Tan

et al. 2020

Mol Cancer

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“…A recent study has demonstrated an increased migration and proliferation rate of cells transfected with CagA, suggesting its role in promoting the malignant transfection of gastric epithelial cells [ 85 ]. Several studies have found an enhanced probability of gastric carcinogenicity and an induction of the epithelial mesenchymal transition (EMT) process caused by CagA-positive H. pylori [ 86 , 87 , 88 ].…”

Section: Caga-dependent Mechanisms Of Pathogenicitymentioning

confidence: 99%

Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity

Ansari

Yamaoka

2020

IJMS

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Helicobacter pylori causes persistent infection in the gastric epithelium of more than half of the world’s population, leading to the development of severe complications such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Several virulence factors, including cytotoxin-associated gene A (CagA), which is translocated into the gastric epithelium via the type 4 secretory system (T4SS), have been indicated to play a vital role in disease development. Although infection with strains harboring the East Asian type of CagA possessing the EPIYA-A, -B, and -D sequences has been found to potentiate cell proliferation and disease pathogenicity, the exact mechanism of CagA involvement in disease severity still remains to be elucidated. Therefore, we discuss the possible role of CagA in gastric pathogenicity.

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“…Interestingly, Helicobacter pylori (H. pylori) and its cytotoxin-associated gene A (CagA) were shown to promote malignant transformation of gastic mucosal epithelial cells. H. pylori impairs DNA mismatch repair and facilitates tumor growth through the induction of miR-155, suggesting that H. pylori, at least partly, mediates carcinogenesis through miR-155 expression in gastric cancer [51,52]. Additionally, H. pylori has been reported to promote carcinogenesis via miR-155 upregulation in a model of gastric mucosa-associated lymphoid tissue (MALT) lymphoma [53].…”

Section: Dysregulation Of Mirs In Ctclmentioning

confidence: 99%

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

Gluud

Willerslev-Olsen

Gjerdrum

et al. 2020

Cancers

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Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.

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Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

Cited by 33 publications

References 46 publications

Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer

Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer

Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

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