Background: Diffuse large B-cell lymphoma (DLBCL) is a type of highly heterogeneous malignancy. Histone deacetylase 1 (HDAC1) plays a key role in various malignancies, but its function remains elusive in DLBCL. This study aims to explore the pivotal role and the mechanism of HDAC1 in DLBCL.

Methods: HDAC1 expression was detected in DLBCL tissues and cells. The glycolytic activity was assessed using pyruvate, lactic acid and glucose consumption assay kits. Cell apoptosis and proliferative capacity were measured by flow cytometry, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Western blotting was used to detect the expression of HDAC1, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and glycolysis-related proteins. The effects of HDAC1 on tumor growth in vivo were explored by establishing a xenotransplantation model. Expressions of HDAC1, Ki-67, and c-myc in mouse tumors were detected by means of immunohistochemistry.

Results: High levels of HDAC1 were found in DLBCL tissues and cells (p < 0.05). HDAC1 knockdown repressed cell proliferation, glycolysis, and PI3K/AKT/mTOR pathway in DLBCL cells (p < 0.05). Moreover, 740Y-P (PI3K/AKT/mTOR pathway activator) partly reversed the inhibition of HDAC1 knockdown on cell proliferation and glycolysis (p < 0.05). Importantly, tumor xenotransplantation models showed that HDAC1 knockdown inhibited tumor growth in vivo (p < 0.05).

Conclusions: HDAC1 facilitates the proliferation and glycolysis of DLBCL by mediating the PI3K/AKT/mTOR pathway, offering a therapeutic target for DLBCL.