Regulation of HACE1 Expression Enhances HDAC Inhibitor Lmk-235-Mediated Apoptosis in Diffuse Large B-Cell Lymphoma Cells

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma (NHL). It is a group of adult lymphomas with a large clinical presentation and prognosis heterogeneity. In order to improve the cure rate of diffuse large B-cell lymphoma, it is necessary to find a new DLBCL treatment plan that can control the progression of the disease and explore its unknown potential therapeutic targets. Epigenetic modification has become a new treatment for leukemia in recent years, and histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL in recent years. However, in addition to effective clinical efficacy, Pan-HDACis has side effects. In contrast, LMK-235 is well tolerated as a novel inhibitor of HDAC4 and HDAC5. HACE1 is a potential tumor suppressor gene located on chromosome 6q21, which is involved in the regulation of tumor cell growth and apoptosis by mediating autophagy and ubiquitination of Rac1. The potential target of HACE1 as an HDAC inhibitor plays an important role in the occurrence, invasion and metastasis of human malignant tumors, but its underlying mechanism of HDACi-mediated apoptosis is still unclear. In this study, we investigated the potential mechanisms by which HACE1 regulates LMK-235-mediated apoptosis in DLBCL cells. In vitro, LMK-235 mediates apoptosis in DLBCL cells in a dose-dependent manner, and up-regulation of HACE1 by lentiviral transfection promotes LMK-235-induced apoptosis. At the same time, high levels of HACE1 can inhibit the expression of HO-1 at mRNA and protein levels. As a previous study in our laboratory, low expression of HO-1 enhanced the apoptotic rate of DLBCL cells. However, the correlation between HACE1 and HO-1 has not been reported. Therefore, we regulated HACE1 levels and found that HACE1 regulates HO-1, which affects the sensitivity of DLBCL cells to LMK-235. Our data show that HACE1 plays a key role in LMK-235-induced apoptosis in DLBCL cells. This provides new hope for the treatment of diffuse large B-cell lymphoma and is a potential new target for the treatment of diffuse large B-cell lymphoma.