Targeting the PLUNC-NLRP3 inflammasome axis could inhibit nasopharyngeal carcinoma lung metastasis

Abstract

Abstract Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx. PLUNC is an early identified secreted protein specifically expressed in the nasopharynx that acts a potential suppresser gene in NPC, but its specific biological role and its mechanism are unclear. We used mRNA-seq combined with RNC-seq to identify the biological role of PLUNC. Tail vein injection of NPC cells to observe the biological role of PLUNC in vivo. The activation of NLRP3 inflammasome was detected by immunoblotting assays and immunofluorescence, and the expression of EMT-related molecules was detected by immunoblotting assays. Then, the migration and invasion were detected by wound healing assay and transwell chamber assay. The mRNA-seq and RNC-seq results showed that PLUNC inhibited NPC progression, and data analysis revealed its correlation with NOD-like receptors. The results confirmed that PLUNC was negatively correlated with NLRP3 inflammasome, and in vivo experiments further elucidated that PLUNC inhibited NPC lung metastasis, and that PLUNC overexpression combined with MCC950 could most effectively inhibit NPC lung metastasis. Our results suggest that PLUNC could inhibit lung metastasis of NPC by suppressing the activation of NLRP3 inflammasome, and targeting the PLUNC-NLRP3 inflammasome axis may provide a new therapeutic strategy for NPC patients.