β-TrCP1 promotes cell proliferation via TNF-dependent NF-κB activation in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL), a heterogeneous group of invasive disease, is the most common type of B-cell non-Hodgkin's lymphomas. The mechanism of its development is closely related to the constitutive activation of NF-κB. In this study, we investigated the function and the mechanism of β-TRCP1 in DLBCL. CCK8 and EdU assays showed that β-TRCP1 could promote the growth of DLBCL cells under the stimulation of TNFα. Furthermore, overexpression of β-TRCP1 enhanced NF-κB activation in the presence of TNFα. Moreover, ectopic expression of β-TRCP1 decreased IκB-α expression but increased phospho-p65 expression. In addition, β-TRCP1 promoted cell cycle progression by accelerating G1-S phase transition. We also found that silencing of β-TrCP1 increased mitoxantrone-induced cell growth arrest and apoptosis. Based on these, we proposed that the expression of β-TRCP1 promoted cell proliferation via TNF-dependent NF-κB activation in DLBCL cells.