Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx. Palate, lung, and nasal epithelium clone (PLUNC) has been identified as an early secreted protein that is specifically expressed in the nasopharynx. The aim of this study was to determine the role and mechanism of PLUNC in NPC. We used mRNA sequencing (seq) combined with ribosome-nascent chain complex (RNC)-seq to determine the biological role of PLUNC. The expression of epithelial-to-mesenchymal transition (EMT)-related molecules was detected by western blotting. Then, cell migration and invasion were detected by wound healing and Transwell chamber assays. NPC cells were injected into the tail vein of nude mice to explore the biological role of PLUNC in vivo. The sequencing results showed that PLUNC inhibited the progression of NPC and its expression was correlated with that of NOD-like receptors. Experiments confirmed that PLUNC inhibited the invasion and metastasis of NPC cells by promoting the ubiquitination degradation of NLRP3. PLUNC overexpression in combination with the treatment by MCC950, an inhibitor of NLRP3 inflammasome activation, was most effective in inhibiting NPC invasion and metastasis. In vivo experiments also confirmed that the combination of PLUNC overexpression and MCC950 treatment effectively inhibited the lung metastasis of NPC cells. In summary, our research suggested that PLUNC inhibited the invasion and metastasis of NPC by inhibiting NLRP3 inflammasome activation, and targeting the PLUNC-NLRP3 inflammasome axis could provide a new strategy for the diagnosis and treatment of NPC patients.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with aberrant host defense responses. However, whether innate immunity is similarly impaired in patients with eosinophilic and those with noneosinophilic CRSwNP remains unclear.
OBJECTIVE: We sought to evaluate the expression and possible modulation of short palate, lung, and nasal epithelium clone 1 (SPLUNC1), an innate immune molecule, in the 2 CRSwNP subsets.
METHODS: Polyp tissue and uncinate processes were collected from 40 patients with CRSwNP, 27 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 22 control subjects. Expression of SPLUNC1; Toll-like receptor (TLR) 2, TLR3, and TLR4; and the proinflammatory cytokines IL-1α, IL-4, IL-13, IL-17A, and IFN-γ was examined in nasal tissues. Additionally, SPLUNC1 expression in response to specific inflammatory stimulation was measured in cultured polyp epithelial cells and A549 cells.
RESULTS: Polyp tissues exhibited significantly decreased expression of SPLUNC1 and other innate immune molecules compared with uncinate process tissues from patients with CRSwNP (P < .05), patients with CRSsNP, and healthy control subjects. Moreover, the eosinophilic CRSwNP subset exhibited significantly decreased SPLUNC1 expression and numbers of submucosal glands, as well as significantly increased IL-4 and IL-13 mRNA levels, compared with the noneosinophilic subset (P < .05). Accordingly, SPLUNC1 expression in polyp epithelial cells was significantly inhibited by IL-4 and IL-13 stimulation in vitro but was significantly upregulated after stimulation with TLR agonists and glucocorticoids (P < .05).
CONCLUSIONS: Differential SPLUNC1 suppression between the eosinophilic and noneosinophilic CRSwNP subsets suggests that they possess distinct pathogenic mechanisms. This finding might benefit the design of appropriate therapeutic interventions targeted to each subset.