Abstract: Objective To investigate the expression of exosome component 5 (EXOSC5) in diffuse large B-cell lymphoma (DLBCL) tissue and its impact on the ferroptosis of DLBCL cells. Methods Immunohistochemistry, RT-qPCR and Western blot were used to detect the expression of EXOSC5 in DLBCL tissues, cell lines (SUDHL4 and OCILY3) and human peripheral blood B lymphocyte cell lines (IM9), the expression of keyferrop- tosisrelated genes including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4(GPX4). Malondialdehyde (MDA) and Fe²⁺ assay kits were used to measure MDA and Fe²⁺ levels in cells. Flow cytometry was used to determine lipid reactive oxygen species (ROS) in cells. CCK8 assay was used to assess cell proliferation and viability. Results Expression of EXOSC5 significantly increased in DLBCL tissues. The expression level of EXOSC5 was higher in SUDHL4 and OCILY3 cells as compared to IM9 cells (P＜0.01). Inhibition of EXOSC5 in SUDHL4 and OCILY3 cells led to a decreased cell proliferation(P＜0.01), down-regulated expression of the key ferroptosis-related genes NRF2, FTH1, and GPX4(P＜0.05)and elevated intracellular levels of MDA, Fe²⁺, and lipid ROS (P＜0.01). These effects could be partially reversed by the ferroptosis inhibitor ferrostatin-1. Knockdown of EXOSC5enhanced cell sensitivity to the ferroptosis inducer RSL3(P＜0.01). Conclusions EXOSC5 is highly expressed in DLBCL and acts as an oncogene. EXOSC5 down regulation might be a target strategy to inhibit malignant proliferation in DLBCL.

Key words: diffuse large B-cell lymphoma, exosome component 5(EXOSC5), ferroptosis