临床神经外科杂志2025，Vol.22Issue(2)：149-157,165,10.DOI:10.3969/j.issn.1672-7770.2025.02.006
TRIM3通过调控PIAS1-STAT1轴抑制胶质瘤发生发展
TRIM3 inhibits glioblastoma progression by regulating the PIAS1-STAT1 axis
摘要
Abstract
Objective To explore the role and molecular mechanisms of TRIM3 in the occurrence and development of human glioblastoma through PIAS1-STAT1.Methods Lentiviral overexpression of TRIM3 and shRNA-transfected GBM cell lines U251 and U87 were constructed,with corresponding control groups CON335 and CON313.The FLAG-TRIM3 plasmid was used to transfect GBM cells and 293T cells,to construct overexpression cell lines.Living cell counting(CCK-8),plate cloning experiments,Transwell chambers,and flow cytometry were used to analyze the proliferative activity,clumping,migration ability,and apoptosis of glioma cells.Western blot and co-immunoprecipitation(Co-IP)experiments were conducted to detect the interaction between TRIM3 and PIAS1 proteins,as well as the specific molecular mechanisms.Real-time quantitative fluorescent polymerase chain reaction(PCR)was used to detect the mRNA expression of TRIM3 and PIAS1.Dual-luciferase reporter gene assays were employed to test the impact of TRIM3 on STAT1 activity.Nude mouse intracranial tumor models were used to demonstrate the impact of TRIM3 on glioma formation in vivo.Results Compared to normal brain tissue cells,the expression of TRIM3 was significantly reduced in GBM tissues.The expression level of TRIM3 decreased with the WHO grades.Overexpression of TRIM3 in glioma cells resulted in a significant attenuation of their proliferative,clumping,and migratory capacities,and induced apoptosis in GBM cells.Western blot analysis revealed that overexpression of TRIM3 in GBM cells was associated with a concentration-dependent reduction in PIAS1 protein levels.Real-time quantitative PCR data indicated that TRIM3 overexpression had no influence on the mRNA levels of PIAS1 and STAT1.Dual-luciferase reporter assays confirmed that TRIM3 enhances the transcriptional activity of STAT1.Moreover,TRIM3 mediated the degradation of PIAS1 by promoting its poly-ubiquitination at the K48 residue,thus alleviating the suppressive effect of PIAS1 on STAT1 transcription.In vivo studies using a nude mouse model demonstrated that,relative to the control group,the rate and size of intracranial tumor formation were significantly reduced in mice with overexpressed TRIM3.Conclusions TRIM3 disrupts the PIAS1-TRIM3 axis,suppressing glioma progression,and offers a novel therapeutic target.关键词
胶质母细胞瘤/TRIM3/PIAS1/STAT1/泛素化Key words
gliobastoma/TRIM3/PIAS1/STAT1/ubiquitination分类
临床医学引用本文复制引用
陈昱宁,焦建同,郭卉,计巍,何其晟,邵君飞..TRIM3通过调控PIAS1-STAT1轴抑制胶质瘤发生发展[J].临床神经外科杂志,2025,22(2):149-157,165,10.基金项目
江苏省卫生健康委2022年度医学科研重点项目(ZD2022038) （ZD2022038）
