Lin Chuanming, Xie Shuiling, Wang Menger, Shen Jianzhen
Department of Hematology, First Affiliated Hospital of Gannan Medical University, No. 128, Jinling Road, Economic Development District, Ganzhou City, Jiangxi Province, 341000, China.
Fujian Medical University Union Hospital, No. 29, Xinquan Road, Gulou District, Fuzhou City, Fujian Province, 350001, China.
BMC Cancer. 2025 Apr 30;25(1):806. doi: 10.1186/s12885-025-14173-1.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma and DLBCL cells are highly sensitive to ferroptosis. The purpose of this research was to evaluate the role and molecular mechanism of peroxiredoxin 1 (PRDX1) on ferroptosis in DLBCL.
The expression of PRDX1 in DLBCL tissues and cells was detected using bioinformatics analysis and reverse transcription quantitative PCR. The impacts of PRDX1 on DLBCL cell proliferation, apoptosis, migration, invasion, and ferroptosis were assessed through a series of in vitro experiments. A xenograft tumor model was constructed to verify the roles of PRDX1 in vivo. Transcriptome sequencing was conducted to identify PRDX1-mediated signaling pathways. Anisomycin, an agonist of mitogen-activated protein kinase (MAPK), was used to explore the modulation of PRDX1 on the MAPK pathway.
PRDX1 expression was upregulated in DLBCL. PRDX1 knockdown inhibited DLBCL cell proliferation, migration, and invasion, promoted apoptosis, and suppressed xenograft tumor growth. PRDX1 knockdown boosted erastin-induced ferroptosis by increasing the levels of iron and MDA, while decreasing the levels of GSH. It also promoted COX2 protein expression and inhibited GPX4 and SLC7A11 protein levels. PRDX1 knockdown reduced the phosphorylation levels of MEK and ERK both under conditions with or without erastin induction. The MAPK/ERK pathway agonist anisomycin, significantly reversed the inhibitory effects of PRDX1 knockdown on the malignant behaviors of DLBCL cells and the promotion of ferroptosis.
PRDX1 knockdown facilitates erastin-induced ferroptosis and obstacles DLBCL progression by inhibiting the MAPK/ERK pathway, offering a potential treatment strategy for DLBCL treatment.
弥漫性大B细胞淋巴瘤（DLBCL）是一种侵袭性淋巴瘤，DLBCL细胞对铁死亡高度敏感。本研究旨在评估过氧化物酶1（PRDX1）在DLBCL铁死亡中的作用及分子机制。
采用生物信息学分析和逆转录定量PCR检测PRDX1在DLBCL组织和细胞中的表达。通过一系列体外实验评估PRDX1对DLBCL细胞增殖、凋亡、迁移、侵袭和铁死亡的影响。构建异种移植肿瘤模型以验证PRDX1在体内的作用。进行转录组测序以鉴定PRDX1介导的信号通路。使用丝裂原活化蛋白激酶（MAPK）激动剂茴香霉素来探究PRDX1对MAPK通路的调节作用。
PRDX1在DLBCL中表达上调。敲低PRDX1可抑制DLBCL细胞增殖、迁移和侵袭，促进凋亡，并抑制异种移植肿瘤生长。敲低PRDX1通过增加铁和丙二醛水平，同时降低谷胱甘肽水平，增强了埃拉司亭诱导的铁死亡。它还促进COX2蛋白表达并抑制GPX4和SLC7A11蛋白水平。在有或没有埃拉司亭诱导的条件下，敲低PRDX1均可降低MEK和ERK的磷酸化水平。MAPK/ERK通路激动剂茴香霉素显著逆转了敲低PRDX1对DLBCL细胞恶性行为的抑制作用以及对铁死亡的促进作用。
敲低PRDX1可促进埃拉司亭诱导的铁死亡，并通过抑制MAPK/ERK通路阻碍DLBCL进展，为DLBCL治疗提供了一种潜在的治疗策略。
