实用肿瘤杂志2026，Vol.41Issue(2)：128-135,8.DOI:10.13267/j.cnki.syzlzz.2026.101
G3BP1通过稳定PD-L1 mRNA抑制肺腺癌细胞的免疫杀伤
G3BP1 inhibits immune killing of lung adenocarcinoma cells by stabilizing PD-L1 mRNA
摘要
Abstract
Objective To explore the role and molecular mechanism of Ras-GTPase-activating protein SH3 domain-binding protein 1(G3BP1),an RNA-binding protein(RBP),in the immune killing process of lung adenocarcinoma cells.Methods The correlation between G3BP1 and programmed death-ligand 1(PD-L1)expressions in lung adenocarcinoma samples was analyzed using data from The Cancer Genome Atlas(TCGA)database.Lentiviral transfection was employed to establish G3BP1-overexpressing lung adenocarcinoma A549 cell model and G3BP1-knockdown lung adenocarcinoma H1975 cell models.Reverse transcription polymerase chain reaction(RT-PCR)and Western blot were performed to detect the mRNA and protein expression levels in the cells,respectively.T cell cytotoxicity assay was used to evaluate the immune killing ability of cytotoxic T lymphocytes(CTLs)against various cell lines.Immunofluorescence-fluorescence in situ hybridization,RNA binding protein immunoprecipitation,and RNA stability assay were conducted to investigate the regulatory mech-anism of G3BP1 on PD-L1 mRNA.The Kaplan-Meier plotter database was utilized to analyze the effect of G3BP1 and PD-L1 expression levels on the prognosis of patients with lung adenocarcinoma.Results TCGA database analysis showed that G3BP1 expression was posi-tively correlated with PD-L1 expression in 526 lung adenocarcinoma samples(r=0.326,P<0.01).The overexpression of G3BP1 promoted the mRNA and protein expressions of PD-L1 in A549 cells(both P<0.05),thereby inhibiting the immune killing effect of CTLs on lung adenocarcinoma cells(P<0.01).The knockdown of G3BP1 suppressed the mRNA and protein expressions of PD-L1 in H1975 cells(both P<0.05),and enhanced the immune killing effect of CTLs(P<0.01).In A549 and H1975 cells,G3BP1 could bind to PD-L1 mRNA and improve its stability,thus promoting PD-L1 protein expression.Kaplan-Meier plotter database analysis revealed that lung adenocarcinoma patients with high expression of either G3BP1 or PD-L1 had significantly shorter overall survival and time to first progression compared with those with low expression(both P<0.01).Conclusions G3BP1 inhibits the immune killing process of lung adenocarcinoma cells by stabilizing PD-L1 mRNA,and its high expression is associated with the poor prognosis of patients.关键词
肺腺癌/程序性死亡受体配体1/Ras-GTP酶激活蛋白SH3结构域结合蛋白1Key words
lung adenocarcinoma/programmed death-ligand 1/Ras-GTPase-activating protein SH3 domain-binding protein 1引用本文复制引用
王雪妮,张兰慧,黄冬薇,钱云峰,董凤英,胡亚惠..G3BP1通过稳定PD-L1 mRNA抑制肺腺癌细胞的免疫杀伤[J].实用肿瘤杂志,2026,41(2):128-135,8.基金项目
广东省医学科学技术研究基金项目(B2022230) （B2022230）
