Abstract
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.
Highlights
MATERIALS AND METHODSGastric cancer (GC), the third most common malignancy, is a primary cause of tumor-related deaths worldwide (Bray et al, 2018)
We further investigated the biological effects of RIPK2 on GC cell proliferation, apoptosis and migration. These findings indicate that RIPK2 plays a vital role in GC cell tumorigenicity and proliferation by regulating nuclear factor κB (NF-κB) signaling and suggest that RIPK2 could be a potential target for GC therapy
RIPK2 is a serine/threonine/tyrosine kinase with a carboxyterminal caspase activation and recruitment domain (Zare et al, 2018), which has been identified as a oncogene participating in several process involved in the development of tumors
Summary
Gastric cancer (GC), the third most common malignancy, is a primary cause of tumor-related deaths worldwide (Bray et al, 2018). We further investigated the biological effects of RIPK2 on GC cell proliferation, apoptosis and migration These findings indicate that RIPK2 plays a vital role in GC cell tumorigenicity and proliferation by regulating NF-κB signaling and suggest that RIPK2 could be a potential target for GC therapy. To further verify the data from GEO, TCGA, and oncomine, we detected the RIPK2 mRNA expression using quantitative reverse transcription- (qRT) PCR. AGS and HGC-27 cells were transfected as described in section “Cell Transfection” and cultured for another 24 h to perform the apoptosis analysis. The cells were stained with 10 μl propidium iodide (Biyuntian, Shanghai, China) for 5 min in the dark and analyzed by flow cytometry (BD Biosciences) to evaluate the rate of apoptosis. Statistical significance was set at P < 0.05 (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, ∗∗∗∗P < 0.0001)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
