Qingqing Wang,1 Chunmei Wang,2,3 Jinlian Chen2,3 1Department of Gastroenterology, Fengxian Hospital, Anhui University of Science and Technology, Shanghai 201499, China; 2Department of Gastroenterology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China; 3Department of Gastroenterology, Shanghai Sixth People’s Hospital (South), Shanghai Jiaotong University, Shanghai 201499, China 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 Parts 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 MIRIN potential application of NLRP6 for gastric cancer treatment.Keywords: NLRP6, H.pylori, cell proliferation, cell apoptosis, gastric cancer .