Chunhong Li , Qiang Wang , Fengsheng Dai , Xinni Xiang , Lin Yi , Bianfei Shao , Qian Li , Xi Peng , Renyan Li , Fang Luo , Zhongjun Wu , Tingxiu Xiang
{"title":"NKAPL通过增强TRIM21蛋白稳定性和进一步抑制NF-κB信号通路抑制NSCLC进展","authors":"Chunhong Li , Qiang Wang , Fengsheng Dai , Xinni Xiang , Lin Yi , Bianfei Shao , Qian Li , Xi Peng , Renyan Li , Fang Luo , Zhongjun Wu , Tingxiu Xiang","doi":"10.1016/j.gendis.2025.101598","DOIUrl":null,"url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) remains a leading cause of mortality in the clinic. Previous studies have demonstrated that the NF-kappa-B activating protein like (NKAPL) is positively correlated with prognosis in several types of cancers. However, the role of NKAPL in the progression of NSCLC remains unclear. The expression and promoter methylation of NKAPL were examined by real-time PCR, quantitative PCR, and methylation-specific PCR. The functional impacts of NKAPL on NSCLC proliferation were explored by CCK8 assay and colony formation assay. Transwell assay was conducted to investigate the role of NKAPL in NSCLC cell migration and invasion, and the influence on metastasis was verified <em>in vivo</em>. Flow cytometry was exploited to analyze the influence on the cell cycle and apoptosis. The regulatory mechanism of NKAPL was investigated by immunoprecipitation-mass spectrometry, western blotting, immunofluorescence, and immunohistochemistry. NKAPL was down-regulated due to promoter methylation, which was associated with poor prognosis in NSCLC patients, while the up-regulation of NKAPL suppressed NSCLC cell proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, the NF-κB signaling pathway was inhibited because the up-regulation of NKAPL increased the stability and expression of TRIM21. NKAPL suppressed NSCLC cell proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em> by increasing the stability and expression of TRIM21 and subsequently inhibiting the NF-κB signaling pathway.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101598"},"PeriodicalIF":6.9000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NKAPL suppresses NSCLC progression by enhancing the protein stability of TRIM21 and further inhibiting the NF-κB signaling pathway\",\"authors\":\"Chunhong Li , Qiang Wang , Fengsheng Dai , Xinni Xiang , Lin Yi , Bianfei Shao , Qian Li , Xi Peng , Renyan Li , Fang Luo , Zhongjun Wu , Tingxiu Xiang\",\"doi\":\"10.1016/j.gendis.2025.101598\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Non-small cell lung cancer (NSCLC) remains a leading cause of mortality in the clinic. Previous studies have demonstrated that the NF-kappa-B activating protein like (NKAPL) is positively correlated with prognosis in several types of cancers. However, the role of NKAPL in the progression of NSCLC remains unclear. The expression and promoter methylation of NKAPL were examined by real-time PCR, quantitative PCR, and methylation-specific PCR. The functional impacts of NKAPL on NSCLC proliferation were explored by CCK8 assay and colony formation assay. Transwell assay was conducted to investigate the role of NKAPL in NSCLC cell migration and invasion, and the influence on metastasis was verified <em>in vivo</em>. Flow cytometry was exploited to analyze the influence on the cell cycle and apoptosis. The regulatory mechanism of NKAPL was investigated by immunoprecipitation-mass spectrometry, western blotting, immunofluorescence, and immunohistochemistry. NKAPL was down-regulated due to promoter methylation, which was associated with poor prognosis in NSCLC patients, while the up-regulation of NKAPL suppressed NSCLC cell proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, the NF-κB signaling pathway was inhibited because the up-regulation of NKAPL increased the stability and expression of TRIM21. NKAPL suppressed NSCLC cell proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em> by increasing the stability and expression of TRIM21 and subsequently inhibiting the NF-κB signaling pathway.</div></div>\",\"PeriodicalId\":12689,\"journal\":{\"name\":\"Genes & Diseases\",\"volume\":\"12 5\",\"pages\":\"Article 101598\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2025-03-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes & Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S235230422500087X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes & Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S235230422500087X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
NKAPL suppresses NSCLC progression by enhancing the protein stability of TRIM21 and further inhibiting the NF-κB signaling pathway
Non-small cell lung cancer (NSCLC) remains a leading cause of mortality in the clinic. Previous studies have demonstrated that the NF-kappa-B activating protein like (NKAPL) is positively correlated with prognosis in several types of cancers. However, the role of NKAPL in the progression of NSCLC remains unclear. The expression and promoter methylation of NKAPL were examined by real-time PCR, quantitative PCR, and methylation-specific PCR. The functional impacts of NKAPL on NSCLC proliferation were explored by CCK8 assay and colony formation assay. Transwell assay was conducted to investigate the role of NKAPL in NSCLC cell migration and invasion, and the influence on metastasis was verified in vivo. Flow cytometry was exploited to analyze the influence on the cell cycle and apoptosis. The regulatory mechanism of NKAPL was investigated by immunoprecipitation-mass spectrometry, western blotting, immunofluorescence, and immunohistochemistry. NKAPL was down-regulated due to promoter methylation, which was associated with poor prognosis in NSCLC patients, while the up-regulation of NKAPL suppressed NSCLC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, the NF-κB signaling pathway was inhibited because the up-regulation of NKAPL increased the stability and expression of TRIM21. NKAPL suppressed NSCLC cell proliferation and metastasis both in vitro and in vivo by increasing the stability and expression of TRIM21 and subsequently inhibiting the NF-κB signaling pathway.
期刊介绍:
Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.
Aims and Scopes
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.