机构：[1]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.华中科技大学同济医学院附属协和医院[2]Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan 430022, China.[3]Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院
Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, with extramedullary myeloma (EMM) being an aggressive form involving malignant infiltration beyond the bone marrow. Copper metabolism is essential for tumor proliferation and metastasis, with copper metabolism MURR1 domain (COMMD) proteins regulating these processes and maintaining copper homeostasis. Dysregulated copper homeostasis contributes to cancer progression, including MM, with elevated copper levels linked to disease aggressiveness and poor prognosis. This study investigates the role of the COMMD3 in mediating MM cell progression, particularly its influence on copper metabolism.Comprehensive bioinformatics analyses were conducted on bone marrow and extramedullary samples to determine the expression of COMMD3, which was validated through in vitro and in vivo functional assays. The MM cell lines RPMI8226 and MM1S underwent lentiviral transfection for COMMD3 overexpression and knockdown. RNA sequencing was conducted on COMMD3 knockdown cells to identify differentially expressed genes. Functional assays measured cell proliferation, migration, apoptosis, and copper metabolism, with a non-obese diabetic severe combined immune-deficiency gamma (NSG) mouse xenograft model providing in vivo validation.Elevated COMMD3 expression was correlated with extramedullary myeloma and poor prognosis in MM patients. COMMD3 promoted MM cell proliferation and migration, modulating intracellular copper levels, likely through the ATOX1-ATP7A-LOX copper-metabolism-related pathway. High ATOX1 expression was correlated with worse outcomes, and ATOX1 inhibition abolished COMMD3's effects.This study highlights the pivotal role of COMMD3 in MM progression, particularly via the ATOX1-ATP7A-LOX axis. These findings provide insights into EMM mechanisms and position COMMD3 as a potential therapeutic target. Future research is needed to validate these findings in larger clinical cohorts and to unravel the precise molecular interactions between COMMD3 and copper metabolism proteins.
基金：
This research was funded by the National Natural Science Foundation of China (No.
82470205 and 82270214).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
无
最新[2023]版：
大类|3 区工程技术
小类|3 区生化与分子生物学3 区医学：研究与实验3 区药学
第一作者：
第一作者机构：[1]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
通讯作者：
通讯机构：[1]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.[2]Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan 430022, China.
推荐引用方式(GB/T 7714)：
Wang Yajun,Zhang Bo,Fan Fengjuan,et al.COMMD3 Regulates Copper Metabolism via the ATOX1-ATP7A-LOX Axis to Promote Multiple Myeloma Progression[J].Biomedicines.2025,13(2):doi:10.3390/biomedicines13020351.
APA：
Wang Yajun,Zhang Bo,Fan Fengjuan,Zhao Fei,Xu Jian...&Hu Yu.(2025).COMMD3 Regulates Copper Metabolism via the ATOX1-ATP7A-LOX Axis to Promote Multiple Myeloma Progression.Biomedicines,13,(2)
MLA：
Wang Yajun,et al."COMMD3 Regulates Copper Metabolism via the ATOX1-ATP7A-LOX Axis to Promote Multiple Myeloma Progression".Biomedicines 13..2(2025)
