Derepressing of STAT3 and USP7 contributes to resistance of DLBCL to EZH2 inhibition.

ABSTRACT: Diffuse large B-cell lymphoma is the most common subtype of lymphoma, representing ∼25 % of non-Hodgkin lymphoid malignancies. EZH2 is highly expressed in Diffuse large B-cell lymphoma and ∼22 % of patients contain EZH2 mutations. EZH2 have been studied as a potential therapeutic target for a decade, but efficient inhibition of EZH2 did not robustly kill lymphoma cells. Here, we found that EZH2 mediates repression of oncogenic genes STAT3 and USP7 in Diffuse large B-cell lymphoma cells. Inhibition of EZH2 leads to upregulation of STAT3 and USP7 at both RNA and protein levels. Along with USP7 upregulation, MDM2 is upregulated and its ubiquitylation substrate, Tumor suppressor P53, is downregulated. Upregulation of STAT3 and downregulation of p53 can strength cell proliferation

SUBMITTER: He C 

PROVIDER: S-EPMC10565777 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature