GYS1通过激活NF-κB通路促进肝细胞癌进展  

GYS1 promotes hepatocellular carcinoma progression by activating the NF-κB pathway

作　　者：王金伟[1] 张立萍 胡石甫[1] 黄涛[1] 刘汉博[1] WANG Jinwei;ZHANG Liping;HU Shifu;HUANG Tao;LIU Hanbo(Department of General Surgery,Tianjin Xiqing Hospital,Tianjin 300380,China)

机构地区：[1]天津市西青医院普外科,天津300380

出　　处：《天津医科大学学报》2024年第5期405-409,421,共6页Journal of Tianjin Medical University

摘　　要：目的:探究糖原合成酶1(GYS1)在原发性肝细胞癌(HCC)进展中的作用。方法:基于GEPIA数据库分析GYS1在肿瘤与癌旁组织的表达差异。从天津市西青医院取20例HCC临床样本。采用RT-PCR、Western印迹及免疫组化验证GYS1基因在肿瘤与癌旁组织的表达差异。对于HCC细胞系,分别转染过表达GYS1质粒及siRNA,采用CCK8、EDU以及划痕实验验证过表达或敲除GYS1后HCC细胞增殖及迁移能力变化。采用Western印迹实验验证过表达或敲除GYS1后核因子(NF)-κB通路的变化。结果:与癌旁组织相比,HCC组织中GYS1表达显著上调(F=30.23,P<0.001);与正常肝细胞相比,肿瘤细胞系中GYS1明显高表达(F=287.35,P<0.001)。基于数据库分析表明,过表达GYS1的HCC患者预后较差(P<0.05)。过表达GYS1在体外促进HCC细胞增殖(F=58.67,P<0.01)及迁移(F=67.34,P<0.01);而敲除GYS1则抑制HCC细胞增殖(F=66.32,P<0.01)及迁移(F=79.24,P<0.01)。RT-PCR及Western印迹结果证实,过表达GYS1可激活NF-κB通路,而敲除GYS1可抑制GYS1通路。结论:HCC组织中GYS1表达量明显升高,并且过表达GYS1,可通过激活NF-κB通路促进HCC进展。Objective:To investigate the role of glycogen synthase1(GYS1)in the process of disease progression in hepatocellular car-cinoma(HCC).Methods:Differential expression of GYS1 in tumor and paracancerous tissues was analyzed based on GEPIA database.A total of clinical samples of primary HCC were obtained from Xiqing Hospital in Tianjin.RT-PCR,Western blotting and immunohisto-chemistry were used to verify the expression difference of GYS1 gene in tumor and paracancer tissues.For HCC lines,overexpression of GYS1 plasmid and siRNA were transfected,and CCK8,EDU and scratch assay were used to verify the changes in the proliferation and migration ability of HCC after overexpression or knockdown of GYS1.Western blotting was used to verify the changes of nuclear factor(NF)-κB pathway after overexpression or knockdown of GYS1.Results:Compared with paraneoplastic tissues,GYS1 expression was significantly upregulated in HCC tissues(F=30.23,P<0.001).Compared with normal hepatocytes,GYS1 was significantly overexpressed in tumor cell lines(F=287.35,P<0.001).Database-based analysis showed that patients with hepatocellular carcinoma overexpressing GYS1 had a poorer prognosis(P<0.05).Overexpression of GYS1 promoted the proliferation(F=58.67,P<0.01)and migration(F=67.34,P<0.01)of HCC cells in vitro,whereas knockdown of GYS1 inhibited the proliferation(F=66.32,P<0.01)and migration(F=79.24,P<0.01)of HCC cells.RT-PCR and Western blotting results confirmed that overexpression of GYS1 activated the NF-κB pathway,whereas knockdown of GYS1 inhibited the NF-κB pathway.Conclusion:The expression of GYS1 in HCC tissues is significantly in-creased,and overexpression of GYS1 can promote the malignant progression of HCC by activating the NF-κB pathway.

关 键 词：肝细胞癌 糖原合成酶1 NF-ΚB 

分 类 号：R735.7[医药卫生—肿瘤]