Cuproptosis-related gene ATOX1 promotes MAPK signaling and diffuse large B-cell lymphoma proliferation via modulating copper transport

Authors

  • Junjie Xie Department of Oncology, General Hospital of Central Theater Command, Wuhan, China
  • Zhixiong Shao Department of Oncology, General Hospital of Central Theater Command, Wuhan, China
  • Changjie Li Jiefang Kairui Medical Laboratory.Building 2, Jinshajiang Road, Jiading District, Shanghai, China
  • Cheng Zeng Department of Oncology, General Hospital of Central Theater Command, Wuhan, China
  • Biao Xu Department of Hematology, General Hospital of Central Theater Command, Wuhan, China

DOI:

https://doi.org/10.17305/bb.2024.10536

Keywords:

Diffuse large B-cell lymphoma, cuproptosis, ATOX1, proliferation, copper transport

Abstract

Diffuse Large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin lymphoma, highlighting the importance of studying susceptibility genes to develop personalized treatment strategies. While cuproptosis, caused by high levels of copper ions induced by ionophores, has been shown to affect cancer survival, its specific role in lymphoma is not yet clear. To investigate the involvement of upregulation-related genes in DLBCL, we employed bioinformatics techniques. Specifically, we analyzed the differentially expressed genes (DEGs) in the GSE25638 dataset using Weighted Gene Co-expression Network Analysis (WGCNA) and performed functional enrichment analysis. By building a Protein-Protein Interaction (PPI) network, candidate genes were identified. Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curve analysis were used to confirm the clinical diagnostic use of these genes. The effects of Antioxidant 1 (ATOX1) knockdown, CuCl2, and DCAC50 treatments on DLBCL cells and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway were investigated by conducting in vitro experiments. Bioinformatics and in vitro experiments confirmed elevated expression of ATOX1 in DLBCL cells and tumor samples. ATOX1 knockdown led to decreased cell proliferation and G2 cell cycle arrest in vitro. Additionally, Phosphorylated Extracellular Signal-Regulated Kinases 1 and 2 (P-ERK1/2) protein levels within the MAPK pathway were reduced as a result of ATOX1 knockdown, but these levels were recovered by CuCl2. Treatment with DCAC50 showed a dose-dependent antiproliferative effect in DLBCL cells, which was strengthened by ATOX1 knockdown. Our study demonstrated that ATOX1 may be important in DLBCL via controlling the MAPK pathway through copper transport, providing new insights into potential therapeutic strategies for DLBCL.

Citations

Downloads

Download data is not yet available.
diffuse large B-cell lymphoma

Downloads

Additional Files

Published

16-07-2024

Issue

Section

Research article

Categories

How to Cite

1.
Cuproptosis-related gene ATOX1 promotes MAPK signaling and diffuse large B-cell lymphoma proliferation via modulating copper transport. Biomol Biomed [Internet]. 2024 Jul. 16 [cited 2024 Oct. 9];. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/10536