PRMT1通过抑制铁死亡促进胶质瘤干细胞的放射抗性。

PRMT1 promotes radiotherapy resistance in glioma stem cells by inhibiting ferroptosis.

作者信息

Li Hong, Qi Xiaoyan, He Lijun, Yang Hao, Ju Haitao

机构信息

Department of Radiation Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) and Affiliated Cancer Hospital of Inner Mongolia Medical University, Huhhot, 010020, Inner Mongolia Autonomous Region, China.

Department of Medical Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) and Affiliated Cancer Hospital of Inner Mongolia Medical University, Huhhot, 010020, Inner Mongolia Autonomous Region, China.

出版信息

Jpn J Radiol. 2025 Jan;43(1):129-137. doi: 10.1007/s11604-024-01651-y. Epub 2024 Sep 10.

DOI:10.1007/s11604-024-01651-y

PMID:39254902

Abstract

PURPOSE

The existence of glioma stem cells (GSCs) in cancer is related to glioma radiotherapy resistance. In this research, the effect of protein arginine methyltransferase 1 (PRMT1) on the radiosensitivity of glioma stem cell (GSC)-like cells, as well as its underlying mechanism, was investigated.

METHODS

GSCs-like cells were analyzed and identified by flow cytometry. The self-renewal capability was evaluated by sphere-forming assay. The PRMT1 expression level in glioblastoma were analyzed using the Gene Expression Profiling Interactive Analysis database. The mRNA and protein were scrutinized by RT-qPCR and western blot, respectively. The radiosensitivity was evaluated by clonogenic survival assay. Ferroptosis was evaluated by detecting the levels of reactive oxygen species, malondialdehyde, Fe, glutathione, and 4-hydroxynonenal.

RESULTS

U87 and SHG44 cells with GSC-like phenotype (GSC-U87 and GSC-SHG44) displayed strong expression of CD133 and nestin versus the glioma cells. GSC-U87 and GSC-SHG44 possess the self-renewal capability. The level of PRMT1 was higher in glioblastoma tumor tissues than in the normal paracancer tissues. Knockdown of PRMT1 enhanced the radiotherapy sensitivity of GSCs-like cells, which was evidenced by reduced survival fraction in GSC-U87 and GSC-SHG44 underwent sh-PRMT1 transfection. But, this effect was attenuated by Fer-1 (a ferroptosis inhibitor) treatment, accompanied by the abatement of ferroptosis.

CONCLUSION

PRMT1 promoted radiotherapy resistance in GSCs-like cells by inhibiting ferroptosis.

摘要

目的

肿瘤中胶质瘤干细胞（GSCs）的存在与胶质瘤放疗抵抗相关。本研究探讨蛋白质精氨酸甲基转移酶1（PRMT1）对胶质瘤干细胞样细胞放射敏感性的影响及其潜在机制。

方法

通过流式细胞术分析和鉴定胶质瘤干细胞样细胞。采用成球试验评估自我更新能力。利用基因表达谱交互式分析数据库分析胶质母细胞瘤中PRMT1的表达水平。分别通过RT-qPCR和蛋白质免疫印迹法检测mRNA和蛋白质。采用克隆形成存活试验评估放射敏感性。通过检测活性氧、丙二醛、铁、谷胱甘肽和4-羟基壬烯醛的水平评估铁死亡。

结果

与胶质瘤细胞相比，具有胶质瘤干细胞样表型的U87和SHG44细胞（GSC-U87和GSC-SHG44）显示出CD133和巢蛋白的强表达。GSC-U87和GSC-SHG44具有自我更新能力。胶质母细胞瘤肿瘤组织中PRMT1水平高于正常癌旁组织。敲低PRMT1可增强胶质瘤干细胞样细胞的放射敏感性，这在转染sh-PRMT1的GSC-U87和GSC-SHG44细胞中存活分数降低得到证实。但是，铁死亡抑制剂Fer-1处理减弱了这种效应，并伴随着铁死亡的减轻。