EZH2 suppresses the chemosensitivity of diffuse large B cell lymphoma via regulating TP53INP1

EZH2 functions as an oncogene in various cancers. However, the role of EZH2 in diffuse large B cell lymphoma (DLBCL) is scarcely reported. This study investigates the potential of EZH2 in DLBCL and the underlying mechanisms. mRNA levels were detected using reverse transcription-quantitative PCR. Protein expression was detected using Western blot. Cell viability was detected using CCK-8 assay. Cell proliferation was detected using methylcellulose colony formation. Cell migration and invasion was detected using transwell. We found that EZH2 is upregulated in DLBCL. EZH2 deficiency effectively enhances the chemosensitivity of DLBCL cells to Glofitamab, manifested by promoting Glofitamab-mediated inhibition in the proliferation, migration, and invasion of DLBCL cells. EZH2 deficiency enhances the apoptosis of DLBCL cells. Mechanistically, EZH2 mediates histone methylation of TP53INP1, resulting in its downregulation in DLBCL. TP53INP1 knockdown antagonizes the effects of EZH2 deficiency and contributes to the aggressiveness of DLBCL cells. In summary, EZH2 inhibits the progression of DLBCL via driving H3K27me3 methylation of TP53INP1. Targeting EZH2 may be a promising strategy for DLBCL.