SENP1 knockdown potentiates the apoptosis, cell cycle arrest, and reduces cisplatin resistance of diffuse large B cell lymphoma cells via inducing ferroptosis.

Abstract

Ferroptosis has been regarded as a critical event in the process of diffuse large B cell lymphoma (DLBCL). Sentrin-specific protease 1 (SENP1) has emerged as an oncogene in multiple human malignancies. The present work was to investigate the effects of SENP1 on the progression of DLBCL and the possible regulatory mechanism involving ferroptosis. SENP1 expression in DLBCL tissues, parental and cisplatin-resistant DLBCL cells were, respectively, tested by GEPIA database, RT-qPCR, and Western blot. Cell viability was estimated via CCK-8 assay. Flow cytometry analysis estimated cell apoptosis and cycle. Western blot examined the expression of apoptosis-, cell cycle-, and ferroptosis-associated proteins. TBARS assay and BODIPY 581/591 C11 probe measured lipid peroxidation. Related assay kit assessed total iron levels. CCK-8 and flow cytometry evaluated cisplatin resistance. SENP1 expression was raised in DLBCL tissues and cells. SENP1 knockdown reduced cell viability, boosted cell apoptosis, cell cycle arrest, and elevated cisplatin sensitivity in DLBCL. SENP1 depletion drove the ferroptosis of both parental and cisplatin-resistant DLBCL cells and ferroptosis inhibitor Fer-1 reversed the influences of SENP1 inhibition on cell viability, apoptosis, cell cycle, and cisplatin resistance in DLBCL. Anyway, SENP1 absence might facilitate ferroptosis to obstruct the development of DLBCL and cisplatin resistance.