USP37 promotes diffuse large B-cell lymphoma progression by deubiquitinating and stabilizing c-myc

J Mol Histol. 2024 Dec 26;56(1):54. doi: 10.1007/s10735-024-10323-0.

Abstract

A poorer prognosis is thought to be associated with "double expressor lymphomas," which are a subtype of diffuse large B cell lymphomas (DLBCL) that co-express MYC and BCL2. While the role of ubiquitin-specific peptidase 37 (USP37) in lung cancer, where it mediates the deubiquitination and stabilization of c-myc, has been well-documented, its involvement in DLBCL remains unexplored. The use of RT-PCR, immunohistochemistry, or WB test allowed for the detection of elevated USP37 in DLBCL tissues and cells. In order to understand the function of USP37 in DLBCL, keloid DLBCL cells were transfected with si-USP37 using Lipofectamine 3000. When tested on DLBCL cells, USP37 increased cell proliferation and inhibited cell cycle progression. USP37 controls the process of deubiquitination to stabilise c-myc proteins. The overexpression of c-Myc facilitated cell proliferation and prevented the cell cycle of DLBCL cells stimulated by si-USP37, which should be taken into consideration. Furthermore, USP37 depletion consistently hinders the development of tumour xenografts in mouse models. Overexpressing c-myc, however, may partially counteract this impact. The data show that USP37 may be a potential therapeutic target for DLBCL, and that it may enhance the course of the disease by deubiquitinating c-myc via direct interactions with c-myc.

Keywords: C-myc; Diffuse large B cell lymphomas; E3 ubiquitin ligase USP37.

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation*
  • Disease Progression*
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / metabolism
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Mice
  • Protein Stability
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins c-myc* / metabolism
  • Ubiquitination*

Substances

  • Proto-Oncogene Proteins c-myc
  • USP37 protein, human
  • Endopeptidases
  • MYC protein, human