NLRP6, decreased in gastric cancer, suppresses tumorigenicity of gastric cancer cells

BACKGROUND: Helicobacter pylori (H. pylori) infection has been regarded as a main risk factor for gastric cancer. Nod-like receptor pyrin domain-containing protein 6 (NLRP6), a component of inflammasome, has been linked to colorectal tumorigenesis. Here, we aimed to evaluate NLRP6 expression profile and functions in gastric cancer. MATERIALS AND METHODS: We examined NLRP6 expression in gastric cancer and adjacent normal gastric tissues. The biological functions and mechanism of NLRP6 overexpression in gastric cancer cells were investigated. RESULTS: Downregulated NLRP6 expression in human gastric cancer significantly correlated with H. pylori infection, tumor size, TNM stage, lymph node metastasis, and overall survival. NLRP6 overexpression in gastric cancer cells led to a significant decrease in cell proliferation, migration, and invasion, as well as a notable increase in cell apoptosis, whereas NLRP6 knockdown had opposing effects. In addition, NLRP6 overexpression significantly repressed STAT3 phosphorylation and the transcription of its target genes, Bcl-2 and MMP-2. Moreover, forkhead box O3 (FOXO3), a transcription factor regulated by H. pylori, was demonstrated as an upstream regulator of NLRP6 transcription. CONCLUSION: Our study may provide insight into the understanding of NLRP6 as a tumor suppressor and implicate the potential application of NLRP6 for gastric cancer treatment.