NFS1, together with FXN, protects cells from ferroptosis and DNA damage in diffuse large B-cell lymphoma

作者：Xue Shi, Yun Zhao, Hongyu Gao, Wei Yang, Jun Liao, Huihan Wang, Xiaotian Wang, Wei Yan · 发表于：Redox Biology · 年份：2025 · DOI：10.1016/j.redox.2025.103878 · 被引用次数：18 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、Circular RNAs in diseases

Diffuse large B cell lymphoma (DLBCL) is a common hematologic malignancy. NFS1 cysteine desulfurase, as a rate-limiting enzyme in the iron-sulfur cluster (ISC) biogenesis, has been reported to be associated with tumor progression. However, the role of NFS1 in DLBCL remains elusive. Here, we showed an upregulation of NFS1 in DLBCL tumor tissues. Knockdown of NFS1 decreased the cell viability and enhanced LDH levels in DLBCL cells. Animal experiments further indicated that downregulation of NFS1 suppresses tumor growth in vivo. NFS1 knockdown increased the lipid reactive oxygen species (ROS) level in cells, and this promotional effect was reversed by ferroptosis inhibitors, but not influenced by other types of cell death inhibitors. This result suggested that NFS1 depletion-impaired cell viability is associated with ferroptosis. Silenced NFS1 aggravated ferroptosis inducers caused cell viability inhibition, lactate dehydrogenase (LDH), and lipid ROS levels enhancement, while the addition of ferroptosis inhibitors abated these trends. Moreover, catalytic residue mutation of NFS1 did not affect its protein expression but decreased the cell viability, which was promoted by NFS1 upregulation, indicating that the protective effect of NFS1 in DLBCL cells was related to its catalytic activity. Further results showed that frataxin (FXN), the upstream activator of NFS1, reduced the cell viability in NFS1 upregulated cells. Consistent with NFS1, FXN silencing aggravated erastin-induced c...