The following is a summary of “Targeting positive cofactor 4 induces autophagic cell death in MYC-expressing diffuse large B-cell lymphoma,” published in April 2023 issue of Experimental Hematology by Ma et al.
Diffuse large B-cell lymphoma (DLBCL) expressing MYC is classified as one of the difficult-to-treat lymphomas. The etiology of DLBCL expressing MYC remains uncertain, and there is a shortage of efficacious treatment options. Positive cofactor 4 (PC4) has been identified as an upstream regulator of c-Myc. In diffuse large B-cell lymphoma (DLBCL), PC4 is overexpressed and is significantly associated with clinical staging, prognosis, and c-Myc expression. Additionally, researchers’ in vivo and in vitro investigations have demonstrated that the depletion of PC4 can trigger autophagic cell death and amplify the healing impact of doxorubicin in MYC-positive diffuse large B-cell lymphoma.
The autophagic cell death due to PC4 knockdown in MYC-expressing DLBCL is attributed to the inhibition of c-Myc-mediated aerobic glycolysis and the activation of the AMPK/mTOR signaling pathway. Using dual-luciferase reporter assay and electrophoretic mobility shift assay, it has been discovered that PC4 exerts its oncogenic properties by directly binding to the promoters of c-Myc. In summary, the researcher’s study offers new knowledge regarding the roles and mechanisms of PC4 in DLBCL expressing MYC. The researcher’s findings indicate that PC4 is a potential therapeutic target for MYC-expressing DLBCL.