安徽医科大学学报2026，Vol.61Issue(4)：662-676,15.DOI:10.19405/j.cnki.issn1000-1492.2026.04.010
FAH通过激活PI3K/AKT/mTOR信号通路促进胶质母细胞瘤进展
FAH promotes glioblastoma progression by activating the PI3K/AKT/mTOR signaling pathway
摘要
Abstract
Objective To investigate the functional role and underlying molecular mechanisms of fumarylacetoac-etate hydrolase(FAH)in the progression of glioblastoma(GBM).Methods Differential expression analysis was performed on the TCGA-GBM,GSE4290,and GSE116520 datasets.Weighted gene co-expression network analy-sis(WGCNA)was used to identify key modules,and Cox regression and risk modeling were used to screen prog-nostic genes.Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels.The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases.The func-tional role of FAH was validated by in vitro and in vivo experiments,and pathway analysis was performed to explore the underlying mechanisms.Results A total of 152 overlapping genes were identified across the three GBM datas-ets(P<0.05).WGCNA revealed that the turquoise module was most strongly associated with tumor purity,stro-mal score,immune score,and ESTIMATE score(P<0.001).Compared with normal tissues,three prognostic genes(C T S D,F A H,and THBD)were upregulated in GBM and correlated with immune infiltration(P<0.05).FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues,and its expression was sig-nificantly associated with age stratification and TP53 mutation(P<0.05).CCK-8 assay results showed that,com-pared with the shNC group,the proliferative activity of GBM cells in the shFAH group was reduced(P<0.001).Transwell migration and invasion assays demonstrated that,relative to the shNC group,the numbers of migrated and invaded cells in the shFAH group decreased(P<0.05).Western blot analysis revealed that the protein expres-sion levels of PI3K,p-AKT,and p-mTOR in the shFAH group decreased compared with those in the shNC group(P<0.05).In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight signifi-cantly decreased in the shFAH group compared with the shNC group(P<0.001).Conclusion FAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic tar-get for GBM.关键词
胶质母细胞瘤/PI3K/AKT/mTOR信号通路/FAH/肿瘤微环境/预后/肿瘤进展Key words
glioblastoma/PI3K/AKT/mTOR signaling pathway/FAH/tumor microenvironment/prognosis/tu-mor progression分类
医药卫生引用本文复制引用
李式浩,李佳,马庆防,赵兵,杨铁牛,杨金亮,张永亮,李仲森,李顺利,陈宁,王建标..FAH通过激活PI3K/AKT/mTOR信号通路促进胶质母细胞瘤进展[J].安徽医科大学学报,2026,61(4):662-676,15.基金项目
安徽省自然科学基金项目(编号:1908085MH284) Natural Science Foundation of Anhui Province(No.1908085MH284) （编号:1908085MH284）
