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

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 u...

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Autores principales: Yang, Qian, Tian, Shan, Liu, Zhengru, Dong, Weiguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900563/
https://www.ncbi.nlm.nih.gov/pubmed/33633788
http://dx.doi.org/10.3389/fgene.2021.627464
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author Yang, Qian
Tian, Shan
Liu, Zhengru
Dong, Weiguo
author_facet Yang, Qian
Tian, Shan
Liu, Zhengru
Dong, Weiguo
author_sort Yang, Qian
collection PubMed
description 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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spelling pubmed-79005632021-02-24 Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer Yang, Qian Tian, Shan Liu, Zhengru Dong, Weiguo Front Genet Genetics 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. Frontiers Media S.A. 2021-02-09 /pmc/articles/PMC7900563/ /pubmed/33633788 http://dx.doi.org/10.3389/fgene.2021.627464 Text en Copyright © 2021 Yang, Tian, Liu and Dong. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yang, Qian
Tian, Shan
Liu, Zhengru
Dong, Weiguo
Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer
title Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer
title_full Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer
title_fullStr Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer
title_full_unstemmed Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer
title_short Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-κB Signaling Pathway in Gastric Cancer
title_sort knockdown of ripk2 inhibits proliferation and migration, and induces apoptosis via the nf-κb signaling pathway in gastric cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900563/
https://www.ncbi.nlm.nih.gov/pubmed/33633788
http://dx.doi.org/10.3389/fgene.2021.627464
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