Lin Chuanming, Xin Liuyan, Xie Shuiling
Department of Hematology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Hematol Oncol. 2025 Mar;43(2):e70054. doi: 10.1002/hon.70054.
Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin's lymphoma (NHL). Ferroptosis is a novel form of cell death involved in multiple tumor development. However, the relationship between ferroptosis-related genes and DLBCL has not been extensively studied. The GSE95290 dataset was downloaded from the Gene Expression Omnibus (GEO) database and merged with genes associated with ferroptosis to screen differentially expressed genes (DEGs). Hub genes were identified by constructing a protein-protein interaction (PPI) network. The messenger RNA (mRNA) expressions of hub genes were subsequently detected in vitro using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The impact of voltage dependent anion channel 1 (VDAC1) on the proliferation, apoptosis, and ferroptosis of DLBCL was evaluated using Cell Counting Kit-8, flow cytometry, and relevant ferroptosis assays, respectively. Six highly expressed hub genes were identified, all of which could be used as diagnostic biomarkers for DLBCL. In vitro studies revealed that suppressing VDAC1 expression inhibited DLBCL cell proliferation and promoted apoptosis. Furthermore, knockdown of VDAC1 promoted ferroptosis in DLBCL cells and xenograft tumor models, resulting in elevated levels of malondialdehyde (MDA) and iron and increased protein levels of Acyl-CoA synthetase long-chain family 4 (ACSL4) and cyclooxygenase-2 (COX2). Conversely, glutathione (GSH) and superoxide dismutase (SOD) levels were reduced, accompanied by decreased protein levels of glutathione peroxidase 4 (GPX4) and ferritin heavy chain1 (FTH1). VDAC1 knockdown induces ferroptosis in DLBCL, which provides new insights into the pathogenic mechanisms of DLBCL.
弥漫性大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤（NHL）中一种常见的亚型。铁死亡是一种参与多种肿瘤发生发展的新型细胞死亡形式。然而，铁死亡相关基因与DLBCL之间的关系尚未得到广泛研究。从基因表达综合数据库（GEO）下载GSE95290数据集，并与铁死亡相关基因合并，以筛选差异表达基因（DEG）。通过构建蛋白质-蛋白质相互作用（PPI）网络来鉴定枢纽基因。随后使用逆转录定量聚合酶链反应（RT-qPCR）在体外检测枢纽基因的信使核糖核酸（mRNA）表达。分别使用细胞计数试剂盒-8、流式细胞术和相关铁死亡检测方法评估电压依赖性阴离子通道1（VDAC1）对DLBCL增殖、凋亡和铁死亡的影响。鉴定出6个高表达的枢纽基因，所有这些基因都可用作DLBCL的诊断生物标志物。体外研究表明，抑制VDAC1表达可抑制DLBCL细胞增殖并促进凋亡。此外，敲低VDAC1可促进DLBCL细胞和异种移植肿瘤模型中的铁死亡，导致丙二醛（MDA）和铁水平升高，酰基辅酶A合成酶长链家族4（ACSL4）和环氧化酶-2（COX2）的蛋白质水平增加。相反，谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平降低，同时谷胱甘肽过氧化物酶4（GPX4）和铁蛋白重链1（FTH1）的蛋白质水平降低。敲低VDAC1可诱导DLBCL中的铁死亡，这为DLBCL的发病机制提供了新的见解。
