KDM2A Targets PFKFB3 for Ubiquitylation to Inhibit the Proliferation and Angiogenesis of Multiple Myeloma Cells

Frontiers in Oncology

Xiaofei Zhao¹  Zhenbo Hu²  Aihong Wang²  Xinling Liu²  Jie Meng²  Zhanju Wang²  Zhen Cai³  Qilu Xu⁴  Jiaqiu Li⁵ 

[1] Department of Dermatology, Weifang Hospital of Traditional Chinese Medicine, Weifang, China;Department of Hematology, Laboratory for Stem Cell and Regenerative Medicine, Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China;Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Department of Hematology, The First Affiliated Hospital, Weifang Medical University, Weifang, China;Department of Oncology, Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China;

关键词: KDM2A;    PFKFB3;    ubiquitination;    multiple myeloma;    proliferation;   

DOI  :  10.3389/fonc.2021.653788

来源: DOAJ

【 摘 要 】

The lysine demethylase KDM2A (also known as JHDM1A or FBXL11) demethylates histone H3 at lysine K36 which lead to epigenetic regulation of cell proliferation and tumorigenesis. However, many biological processes are mediated by KDM2A independently by its histone demethylation activity. In the present study, we aimed to characterize the functional significance of KDM2A in multiple myeloma (MM) disease progression. Specifically, we defined that one of the key enzymes of glycolysis PFKFB3 (6-phosphofructo-2-kinase) is ubiquitylated by KDM2A which suppresses MM cell proliferation. Previous study showed that KDM2A and PFKFB3 promoted angiogenesis in various tumor cells. We further reveal that KDM2A targets PFKFB3 for ubiquitination and degradation to inhibit angiogenesis. Several angiogenic cytokines are also downregulated in MM. Clinically, MM patients with low KDM2A and high PFKFB3 levels have shown worse prognosis. These results reveal a novel function of KDM2A through ubiquitin ligase activity by targeting PFKFB3 to induce proliferation, glycolysis and angiogenesis in MM cells. The data provides a new potential mechanism and strategy for MM treatment.

【 授权许可】

Unknown