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目的通过研究高尔基蛋白73(GP73)对炎症反应的影响,揭示其参与肿瘤发生发展可能的机制。方法基于TCGA数据库中肝癌患者的GP73与炎症因子NF-κB、IL-1β、IL-6、TNF-α等基因表达相关性的分析,推测GP73可能参与炎症反应。依据数据分析结果设计细胞实验,构建过表达GP73的质粒和敲低GP73的小干扰RNA(siRNA),通过检测野生型、过表达和敲低表达GP73细胞系中NF-κB的转录活性以及炎症因子IL-1β、IL-6、TNF-α等基因的表达,来验证GP73在炎症反应中发挥的作用。结果 TCGA数据库分析结果提示,临床肝癌患者的GP73基因表达与NF-κB、IL-1β、IL-16及TNF-α的表达均呈正相关;细胞实验结果显示,过表达GP73细胞系与野生型相比,细胞内NF-κB转录活性升高,而敲低GP73细胞系内NF-κB转录活性降低;过表达GP73细胞系与野生型相比细胞内IL-1β、IL-6及TNF-α的表达均升高;二硫代氨基甲酸吡咯烷(PDTC)能抑制GP73激活炎症反应,NF-κB为GP73激活炎症反应的关键分子。结论 GP73可能参与炎症反应,并因此促进肿瘤的发生发展。
OBJECTIVE: To study the effect of GP73 on inflammation and to reveal its possible mechanism involved in tumorigenesis. Methods Based on the analysis of the correlation between the expression of GP73 and inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α in patients with hepatocellular carcinoma in the TCGA database, GP73 may be involved in the inflammatory response. According to the results of data analysis, we designed the cell experiment, constructed the GP73 overexpression plasmid and knockdown GP73 small interfering RNA (siRNA), and detected the transcriptional activity of NF-κB in GP73 cell line by overexpression and knockdown, IL-1β, IL-6, TNF-α and other genes to verify the role of GP73 in the inflammatory response. Results The results of TCGA database indicated that there was a positive correlation between the expression of GP73 gene and the expression of NF-κB, IL-1β, IL-16 and TNF-α in clinical hepatocellular carcinoma patients. The results of cell assay showed that GP73 cell line overexpressed The intracellular transcription of NF-κB was increased, but the transcriptional activity of NF-κB was decreased in GP73 knockdown cells. The overexpression of GP73 in the GP73 cells compared with the wild-type (PDTC) could inhibit the GP73 activation of inflammatory response, NF-κB GP73 activation of the inflammatory response of the key molecules. Conclusion GP73 may be involved in the inflammatory response, and thus promote the development of tumors.