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  2. PLUNC inhibits invasion and metastasis in nasopharyngeal carcinoma by inhibiting NLRP3 inflammasome activation

PLUNC inhibits invasion and metastasis in nasopharyngeal carcinoma by inhibiting NLRP3 inflammasome activation

  • Biochim Biophys Acta Mol Basis Dis. 2024 Jul 14;1870(7):167352. doi: 10.1016/j.bbadis.2024.167352.
Qing Zhou 1 Yilin Guo 2 Ziying Tian 2 Yanbing Qiu 3 Ying Liu 4 Qingluan Liu 5 Yijun Liu 6 Yuqin Yang 7 Lei Shi 8 Xiayu Li 9 Ge Gao 2 Songqing Fan 8 Zhaoyang Zeng 10 Wei Xiong 10 Ming Tan 11 Guiyuan Li 10 Wenling Zhang 12
Affiliations

Affiliations

  • 1 Department of Medical Laboratory Science, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Clinical Laboratory, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China; Department of Medical Laboratory Science, Xiangya Medical College, Central South University, Changsha, Hunan, China.
  • 2 Department of Medical Laboratory Science, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Medical Laboratory Science, Xiangya Medical College, Central South University, Changsha, Hunan, China.
  • 3 Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 4 Department of Clinical Laboratory, Zhengzhou Orthopaedics Hospital, Zhengzhou, Henan, China.
  • 5 Changsha Hospital for Maternal and Child Health Care, Changsha, Hunan, China.
  • 6 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 7 Shenzhen Maternity & Child Healthcare Hospital Clinical Laboratory, Shenzhen, Guangdong, China.
  • 8 Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 9 Hunan Provincial People's Hospital, Changsha, Hunan, China.
  • 10 NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China.
  • 11 Graduate Institute of Biomedical Sciences, China Medical University, Taiwan; Research Center for Cancer Biology, China Medical University, Taiwan.
  • 12 Department of Medical Laboratory Science, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Medical Laboratory Science, Xiangya Medical College, Central South University, Changsha, Hunan, China. Electronic address: zhangwenling73@126.com.
Abstract

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.

Keywords

Metastasis; NLRP3; Nasopharyngeal carcinoma; PLUNC; Ubiquitination.

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