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

IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chunhong Li , Qiang Wang , Fengsheng Dai , Xinni Xiang , Lin Yi , Bianfei Shao , Qian Li , Xi Peng , Renyan Li , Fang Luo , Zhongjun Wu , Tingxiu Xiang
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引用次数: 0

摘要

非小细胞肺癌(NSCLC)仍然是临床死亡的主要原因。先前的研究已经证明NF-kappa-B激活蛋白样蛋白(NKAPL)与几种类型癌症的预后呈正相关。然而,NKAPL在NSCLC进展中的作用尚不清楚。采用实时PCR、定量PCR和甲基化特异性PCR检测NKAPL的表达和启动子甲基化。通过CCK8实验和集落形成实验探讨NKAPL对NSCLC增殖的功能影响。Transwell实验研究NKAPL在NSCLC细胞迁移和侵袭中的作用,并在体内验证其对转移的影响。利用流式细胞术分析其对细胞周期和凋亡的影响。采用免疫沉淀-质谱法、免疫印迹法、免疫荧光法和免疫组织化学方法研究NKAPL的调控机制。NKAPL由于启动子甲基化而下调,这与NSCLC患者预后不良有关,而NKAPL的上调在体外和体内均抑制NSCLC细胞的增殖和转移。机制上,由于NKAPL的上调增加了TRIM21的稳定性和表达,NF-κB信号通路受到抑制。NKAPL通过增加TRIM21的稳定性和表达,进而抑制NF-κB信号通路,在体外和体内抑制NSCLC细胞的增殖和转移。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
Genes & Diseases
Genes & Diseases Multiple-
CiteScore
7.30
自引率
0.00%
发文量
347
审稿时长
49 days
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.
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