PLUNC 通过抑制 NLRP3 炎性体激活来抑制鼻咽癌的侵袭和转移。
PLUNC inhibits invasion and metastasis in nasopharyngeal carcinoma by inhibiting NLRP3 inflammasome activation.
发表日期：2024 Jul 12
作者：
Qing Zhou, Yilin Guo, Ziying Tian, Yanbing Qiu, Ying Liu, Qingluan Liu, Yijun Liu, Yuqin Yang, Lei Shi, Xiayu Li, Ge Gao, Songqing Fan, Zhaoyang Zeng, Wei Xiong, Ming Tan, Guiyuan Li, Wenling Zhang
来源：
Bba-Mol Basis Dis
摘要：
鼻咽癌（NPC）是发生在鼻咽部的恶性肿瘤。腭、肺和鼻上皮克隆 (PLUNC) 已被确定为一种在鼻咽中特异性表达的早期分泌蛋白。本研究的目的是确定 PLUNC 在 NPC 中的作用和机制。我们使用 mRNA 测序 (seq) 结合核糖体新生链复合物 (RNC)-seq 来确定 PLUNC 的生物学作用。通过蛋白质印迹法检测上皮间质转化（EMT）相关分子的表达。然后，通过伤口愈合和Transwell小室实验检测细胞迁移和侵袭。将NPC细胞注射到裸鼠尾静脉中，探讨PLUNC在体内的生物学作用。测序结果显示PLUNC抑制NPC的进展，其表达与NOD样受体相关。实验证实PLUNC通过促进NLRP3泛素化降解来抑制鼻咽癌细胞的侵袭和转移。 PLUNC过表达与NLRP3炎性体激活抑制剂MCC950联合治疗在抑制NPC侵袭和转移方面最为有效。体内实验也证实，PLUNC过表达与MCC950联合治疗可有效抑制鼻咽癌细胞的肺转移。综上所述，我们的研究表明，PLUNC通过抑制NLRP3炎症小体激活来抑制鼻咽癌的侵袭和转移，靶向PLUNC-NLRP3炎症小体轴可以为鼻咽癌患者的诊断和治疗提供新策略。版权所有©2024。由Elsevier出版B.V.
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.Copyright © 2024. Published by Elsevier B.V.