Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma.

Abstract:

:Inflammasomes can identify endogenous danger signals as an inflammatory immune response. As the most common inflammasome, the NLR pyrin family domain containing 3 (NLRP3) inflammasome is associated with the pathogenesis of different tumors. However, the function of the NLRP3 inflammasome in esophageal cancer (EC) has rarely been reported. Herein, the expression levels of the components of NLRP3 inflammasome and Ki‑67 were analyzed by immunohistochemistry. Furthermore, correlations between the NLRP3 inflammasome and Ki‑67 along with the clinicopathological features of EC patients were evaluated. The components of the NLRP3 inflammasome were also assessed by western blot analysis and quantitative PCR. NLRP3 was silenced or overexpressed in different esophageal squamous cell carcinoma (ESCC) cell lines, and cell viability, migration and invasion were assessed by CCK‑8 and Transwell assays. The present results showed that high NLRP3 expression in the tumor specimens was significantly associated with TNM stage and T category. Spearman's correlation analysis revealed a positive correlation between NLRP3 and the Ki‑67 proliferation index. The mRNA and protein levels of NLRP3, apoptosis‑associated speck‑like protein containing a CARD (ASC), cleaved caspase‑1, and interleukin (IL)‑1β in tumor tissues were higher than those in non‑cancerous tissues. The level of secreted IL‑1β in tumor tissues was also increased, as compared to that in normal tissues. Silencing of NLRP3 in KYSE‑70 and TE13 cells strongly attenuated cell viability, decreased cell mobility in wound‑healing assays and greatly diminished the ability of cell migration and invasion in the Transwell system. Overexpression of NLRP3 in KYSE‑510 and EC9706 cells markedly promoted the proliferation, migration and invasion. Collectively, these results revealed that the the NLRP3 inflammasome is upregulated in human ESCC tissues and promotes ESCC progression. Hence, NLRP3 could be a promising new candidate diagnostic and prognostic target.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Yu S,Yin JJ,Miao JX,Li SG,Huang CZ,Huang N,Fan TL,Li XN,Wang YH,Han SN,Zhang LR

doi

10.3892/or.2020.7493

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

1113-1124

issue

4

eissn

1021-335X

issn

1791-2431

journal_volume

43

pub_type

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