Wang Jian, Luo Xiaolin, Liu Dehua
Department of Pathology, Ganzhou People's Hospital, Ganzhou, Jiangxi, China.
Party Committee Office, The Third Affiliated Hospital of Gannan Medical University/Affiliated stomatological hospital, Ganzhou, Jiangxi, China.
Cell Cycle. 2023 Oct;22(20):2264-2279. doi: 10.1080/15384101.2023.2286782. Epub 2023 Dec 15.
Ferroptosis acts as an important regulator in diverse human tumors, including the glioma. This study aimed to screen potential ferroptosis-related genes involved in the progression of glioma.
Differently expressed genes (DEGs) were screened based on GSE31262 and GSE12657 datasets, and ferroptosis-related genes were separated. Among the important hub genes in the protein-protein interaction networks, HNRNPM was selected as a research target. Following the knockdown of HNRNPM, the viability, migration, and invasion were detected by CCK8, wound healing, and transwell assays, respectively. The role of HNRNPM knockdown was also verified in a xenograft tumor model in mice. Immunohistochemistry detected the expression levels of HNRNPM and Ki67. Moreover, the ferroptosis was evaluated according to the levels of iron, glutathione peroxidase (GSH), and malondialdehyde (MDA), as well as the expression of PTGS2, GPX4, and FTH1.
Total 41 overlapping DEGs relating with ferroptosis and glioma were screened, among which 4 up-regulated hub genes (HNRNPM, HNRNPA3, RUVBL1, and SNRPPF) were determined. The up-regulation of HNRNPM presented a certain predictive value for glioma. In addition, knockdown of HNRNPM inhibited the viability, migration, and invasion of glioma cells in vitro, and also the tumor growth in mice. Notably, knockdown of HNRNPM enhanced the ferroptosis in glioma cells. Furthermore, HNRNPM was positively associated with SMARCA4 in glioma.
Knockdown of HNRNPM inhibits the progression of glioma via inducing ferroptosis. HNRNPM is a promising molecular target for the treatment of glioma via inducing ferroptosis. We provided new insights of glioma progression and potential therapeutic guidance.
铁死亡在包括胶质瘤在内的多种人类肿瘤中起着重要的调节作用。本研究旨在筛选参与胶质瘤进展的潜在铁死亡相关基因。
基于GSE31262和GSE12657数据集筛选差异表达基因（DEGs），并分离出铁死亡相关基因。在蛋白质-蛋白质相互作用网络中的重要枢纽基因中，选择HNRNPM作为研究靶点。在敲低HNRNPM后，分别通过CCK8、伤口愈合和Transwell实验检测细胞活力、迁移和侵袭能力。在小鼠异种移植瘤模型中也验证了敲低HNRNPM的作用。免疫组织化学检测HNRNPM和Ki67的表达水平。此外，根据铁、谷胱甘肽过氧化物酶（GSH）、丙二醛（MDA）水平以及PTGS2、GPX4和FTH1的表达来评估铁死亡情况。
共筛选出41个与铁死亡和胶质瘤相关的重叠DEGs，其中确定了4个上调的枢纽基因（HNRNPM、HNRNPA3、RUVBL1和SNRPPF）。HNRNPM的上调对胶质瘤具有一定的预测价值。此外，敲低HNRNPM可抑制胶质瘤细胞在体外的活力、迁移和侵袭，以及小鼠体内的肿瘤生长。值得注意的是，敲低HNRNPM可增强胶质瘤细胞中的铁死亡。此外，在胶质瘤中HNRNPM与SMARCA4呈正相关。
敲低HNRNPM通过诱导铁死亡抑制胶质瘤的进展。HNRNPM是通过诱导铁死亡治疗胶质瘤的一个有前景的分子靶点。我们为胶质瘤的进展提供了新的见解和潜在的治疗指导。
