Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility

Ota, Masafumi; Tahara, Tomomitsu; Otsuka, Toshimi; Wu, Jing; Nomura, Tomoe; Hayashi, Ranji; Shimasaki, Takeo; Nakamura, Masakatsu; Shibata, Tomoyuki; Arisawa, Tomiyasu

doi:10.3892/ol.2018.7785

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…Although the role of RIPK2 in cancer development has been investigated, especially in colorectal cancer ( Chen et al, 2020 ), its function in GC is not yet clear. Only one study has suggested that the carriers of RIPK2 single nucleotide polymorphism rs16900627 minor allele may have a higher risk for the progression of gastric cancer ( Ota et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer

et al. 2021

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RIPK2 is a 62 kDa protein and a member of the receptor interacting protein kinases (RIPK) family. It was previously demonstrated that RIPK2 might play a role in promoting malignant tumor progression; however, the precise function of RIPK2 in the onset and progression of gastric cancer (GC) remains unclear. In the current study, we investigated the role of RIPK2 in GC. First, we explored the expression levels of RIPK2 in multiple cancers, including GC, using a bioinformatics approach. We constructed the RIPK2-associated protein-protein interaction network using the search tool for the retrieval of interacting genes/proteins for gene ontology and Kyoto encyclopedia of genes and genomes analysis. Next, we compared the RIPK2 expression levels between GC cells and normal gastric mucosal epithelial cell (GES-1) using reverse transcription quantitative PCR analysis. We downregulated the expression of RIPK2 in GC cells to determine the effects of RIPK2 on cell growth, migration, and apoptosis. Finally, we used western blotting to investigate the RIPK2 downstream signaling pathway involved in the regulation of GC progression. Our results showed that RIPK2 was overexpressed in various tumor tissues, including GC, compared to non-cancer tissues. Moreover, RIPK2 expression was significantly upregulated in all four GC cell lines (MGC-803,SGC-7901, HGC-27 and AGS) comparing the GES-1 cells. Silencing of RIPK2 suppressed GC cell growth by inhibiting migration, and inducing apoptosis through the nuclear factor-κB (NF-κB) signaling pathway. In summary, we demonstrate that RIPK2 plays an important role in modulating GC cell proliferation, migration, and apoptosis through the NF-κB signaling pathway. Therefore, RIPK2 functions as a potential oncogene. We believe that RIPK2 can be used as a candidate biomarker, as well as a diagnostic tool, and the therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer

et al. 2021

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“…Previous studies have shown that RIPK2 might be responsible for the chronic in ammation of In ammatory Bowel Disease (IBD) (28,29), and the high level of RIPK2 expression was associated with advanced tumor and metastasis of in ammatory breast cancer (30). It has also been reported that RIPK2 polymorphisms were related to tumor in ltration stages, lymph node metastasis and survival in urothelial bladder cancer (31) and the susceptibility of gastric cancer (32).…”

Section: Discussionmentioning

confidence: 99%

High Expression of RIPK2 is Associated with Taxol Resistance in Serous Ovarian Cancer

Shen¹,

Lin²,

Chen³

et al. 2021

Preprint

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BackgroundTaxol resistance of serous ovarian cancer is responsible for its poor prognosis, yet the underlying mechanism was still poorly understood. Thus, we probed the mechanism of taxol resistance in serous ovarian cancer with multiple bioinformatic methods to provide novel insights for potential therapy. MethodsThe differentially expressed genes (DEGs) and their relationship with overall survival (OS) and progress-free interval (PFI) of ovarian cancer patients were analyzed using gene expression datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The role of receptor interacting serine/threonine kinase 2 (RIPK2) was validated by identifying its co-expressed genes, making function analysis and generating protein-protein network (PPI). Single-sample GSEA (ssGSEA) method was used to explore the immune infiltration and genomic alterations of RIPK2 was also analyzed via cBio Cancer Genomics Portal (cBioProtal).ResultsRIPK2 was highly expressed in taxol resistant ovarian cancer cell lines, while its high expression was also linked with OS and PFI in serous ovarian cancer patients. The PPI network analysis and pathway analysis demonstrated that RIPK2 might take part in positive regulation of NF-κB transcription factor activity. Different expression level of RIPK2 was related to tumor microenvironment alteration, which might participate in formation of taxol resistance.ConclusionsOur studies suggested that high expression of RIPK2 was related to taxol resistance in serous ovarian cancer, while RIPK2 induced taxol resistance through NOD1/RIPK2/NF-κB inflammatory pathway activation and tumor microenvironment changes.

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“…The gastric pathogen Helicobacter pylori is subject to degradation by autophagy via the NOD1/RIPK2 signaling axis. H. pylori infection has long been implicated in the development of gastric cancer [ [178] , [179] , [180] ], and recently, polymorphisms in RIPK2 were found to be associated with increased susceptibility to gastric cancer in Japanese populations [ 181 ] where the prevalence of this disease is very high. Indeed, Nod1 −/− mice are highly susceptible to H. pylori infection [ 182 ], and mechanistically, Irving et al [ 149 ] demonstrated that in gastric epithelial cells, RIPK2 mediates NOD1-dependent IL-8 production and autophagosome formation in early endosomes in response to H. pylori- derived outer membrane vesicles (OMVs) containing PGN.…”

Section: Ripk2 Signaling In Pathogen Infectionmentioning

confidence: 99%

The diverse roles of RIP kinases in host-pathogen interactions

Eng

Wemyss

Pearson

2021

Seminars in Cell & Developmental Biology

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Receptor Interacting Protein Kinases (RIPKs) are cellular signaling molecules that are critical for homeostatic signaling in both communicable and non-communicable disease processes. In particular, RIPK1, RIPK2, RIPK3 and RIPK7 have emerged as key mediators of intracellular signal transduction including inflammation, autophagy and programmed cell death, and are thus essential for the early control of many diverse pathogenic organisms. In this review, we discuss the role of each RIPK in host responses to bacterial and viral pathogens, with a focus on studies that have used pathogen infection models rather than artificial stimulation with purified pathogen associated molecular patterns. We also discuss the intricate mechanisms of host evasion by pathogens that specifically target RIPKs for inactivation, and finally, we will touch on the controversial issue of drug development for kinase inhibitors to treat chronic inflammatory and neurological disorders, and the implications this may have on the outcome of pathogen infections.

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Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility

Cited by 12 publications

References 28 publications

Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer

Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer

High Expression of RIPK2 is Associated with Taxol Resistance in Serous Ovarian Cancer

The diverse roles of RIP kinases in host-pathogen interactions

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