过表达三结构域蛋白48调控p-ERK1/2抑制胶质瘤生长的作用机制  

Researches on the Mechanism of Overexpression of Tripartite Motif Protein 48 Regulating p-ERK1/2 to Inhibit Glioma Growth

作　　者：姜右川 余妍 赵国[1] 李世存 丁鹏[1] JIANG Youchuan;YU Yan;ZHAO Guo;LI Shicun;DING Peng(Dept.of Neurosurgery,The 1st Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650032,China)

机构地区：[1]昆明医科大学第一附属医院神经外科,云南昆明650032

出　　处：《昆明医科大学学报》2024年第5期29-36,共8页Journal of Kunming Medical University

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项重点基金资助项目(202001AY070001-160);云南省卫生高层次人才专项基金资助项目(L-2019020)。

摘　　要：目的探究过表达三结构域蛋白48(tripartite motif protein,TRIM)对胶质瘤生长的影响及其相关机制。方法将12只裸鼠随机均分为2组,分别接种过表达TRIM48的U87胶质瘤稳转株(oeTRIM48组)及其对照细胞株(Vector组)。接种后每3 d测定肿瘤体积,4周后取出肿瘤组织并记录瘤重。肿瘤组织做HE染色,并通过免疫荧光法检测Ki-67的表达,使用Western blot和免疫组化分别检测裸鼠肿瘤和人胶质瘤组织芯片中的TRIM48、ERK1/2和p-ERK1/2水平。结果oeTRIM48组裸鼠肿瘤体积、重量比Vector组裸鼠明显降低(P<0.0001);HE染色结果显示oeTRIM48组细胞核减小、核分裂象减少;Ki-67阳性区域显著降低(P<0.0001),而且oeTRIM48组p-ERK1/2蛋白水平比Vector组显著降低(P<0.01)。组织芯片免疫组化显示,TRIM48和p-ERK1/2在癌旁组织分别呈高表达和低表达,在肿瘤组织则相反。结论过表达TRIM48能够抑制胶质瘤生长、增殖,其作用机制可能与ERK1/2信号通路有关。Objective To investigate the impact of TRIM48 overexpression on glioma and explore the underlying mechanism.Methods Twelve nude mice were randomly assigned into two groups:one inoculated with U87 glioma cells stably overexpressing TRIM48(oeTRIM48 group)and the other with the control cell line(Vector group).Tumor volume was measured every 3 days post-inoculation,and after 4 weeks,the tumors were excised and weighed.Tumor tissues underwent hematoxylin and eosin(H&E)staining,and Ki-67 expression was assessed using immunofluorescence.Additionally,the expressions of TRIM48,ERK1/2,and phosphorylated ERK1/2(p-ERK1/2)in the tumors of nude mice and human glioma tissue arrays were analyzed through Western blot and immunohistochemistry respectively.Results Compared to the Vector group,the oeTRIM48 group exhibited significantly reduced tumor volume and weight(P<0.0001).H&E staining indicated a decrease in nuclei and mitotic count in the oeTRIM48 group.Furthermore,Ki-67 expression was significantly lower in the oeTRIM48 group than that in the Vector group(P<0.0001).The oeTRIM48 group also showed a significantly lower expression of p-ERK1/2 protein compared to the Vector group(P<0.01).Immunohistochemistry on tissue microarrays revealed the high expression of TRIM48 and low expression of p-ERK1/2 in adjacent non-tumoral tissues,with the opposite pattern observed in tumor tissues.Conclusion Overexpression of TRIM48 inhibits the growth and proliferation of glioma,potentially through modulation of the ERK1/2 signaling pathway.

关 键 词：TRIM48 胶质瘤 ERK1/2 

分 类 号：R739.41[医药卫生—肿瘤]