AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025180160
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ORIGINAL RESEARCH ARTICLE

Targeted inhibition of chondroitin polymerizing factor suppresses CD5+ diffuse large B-cell lymphoma progression through the PI3K/AKT signaling and RhoA/ROCK axis

Jingren Lin1 ,  Li Ban2 ,  Lihua Xu1 ,  Sihui Chen2 ,  Jianbo Liu2 ,  Jianli Tang2 ,  Jiayu Huang2 ,  Ao Chen2 ,  Runhui Zheng2*
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1 Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
2 Department of Hematology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
EJMO, 025180160 https://doi.org/10.36922/EJMO025180160
Received: 30 April 2025 | Revised: 15 June 2025 | Accepted: 9 July 2025 | Published online: 25 August 2025
(This article belongs to the Special Issue Tumor Immune Microenvironment and Intervention Strategies)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Diffuse large B-cell lymphoma (DLBCL), particularly the cluster of differentiation (CD) 5+ subtype, presents unique challenges due to its high aggressiveness and limited therapeutic responsiveness.

Objective: This study focuses on chondroitin polymerizing factor (CHPF), a key enzyme in chondroitin sulfate biosynthesis, which has been observed to be upregulated in CD5+ DLBCL tissues and cell lines.

Methods: CHPF expression in DLBCL and normal tissues was compared using tissue microarrays and immunohistochemical analysis. The effects of CHPF knockdown on lymphoma cell proliferation, migration, apoptosis, and the cell cycle were evaluated in vitro using human lymphoma cell lines. In addition, a xenograft mouse model was employed to assess the impact of CHPF knockdown on in vivo tumor growth. Signaling pathways regulated by CHPF, particularly the phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway, were identified through KEGG pathway enrichment analysis. The interaction between CHPF and Ras homolog family member A (RhoA) proteins was investigated using a PMSCV-HA-CHPF overexpression plasmid.

Results: A significantly elevated level of CHPF was observed in DLBCL specimens compared to normal lymphoid tissue, especially in CD5+ cases. CHPF knockdown markedly suppressed lymphoma cell growth and motility, enhanced apoptotic signaling, and induced cell cycle arrest. In vivo, CHPF knockdown restricted lymphoma progression in the xenograft mouse model. Furthermore, CHPF was found to activate the PI3K/AKT signaling pathway and interact with the RhoA protein.

Conclusion: CHPF plays a pivotal role in DLBCL progression by modulating PI3K/AKT signaling pathways. Targeting CHPF may offer a novel therapeutic approach for treating DLBCL.

Graphical abstract
Keywords
Chondroitin polymerizing factor
B-cell lymphoma
CD5
Diffuse large B-cell lymphoma
PI3K/AKT
Funding
This study was funded by the Guangdong Medical Science and Technology Research Foundation (No. 20221110173018595), the Guangzhou Municipal Science and Technology Bureau City-University (Institute) (No. 2024A03J0070), and the Guangzhou Major Medical Disciplines Project (2025 - 2027).
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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