高尔基蛋白73参与炎症反应的分子机制研究

摘要

Objective To study the effect of Golgi protein 73(GP73) on inflammation, and to reveal the effect of GP73 on tumorigenesis and metastasis.Methods The transcriptional activity of NF-κB and the expression of IL-1β, IL-6 and TNF-αwith GP73 overexpression or knockdown were detected to illuminate the role of GP73 in inflammation.According to the TCGA database, the correlation between the transcriptional activity of GP73 and the expression of NF-κB, IL-1β, IL-6 and TNF-αwas analyzed to determine the role of GP73 in tumor inflammation.Results Correlative analysis showed that there was a positive correlation between the expression of GP73 with NF-κB, IL-1β, IL-6 and TNF-α.The transcriptional activity of NF-κB was upregulated by GP73 overexpression, but downregulated by GP73 knockdown.The expression of IL-1β, IL-6 and TNF-αwas upregulated by GP73 overexpression.Ammonium pyrrolidinedithiocarbamate ( PDTC ) was in-volved in inflammation reaction induced by GP73.Conclusion GP73 is possibly involved in inflammation and promotes tu-morigenesis and metastasis.%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。