The Diverse Roles of Histone Demethylase KDM4B in Normal and Cancer Development and Progression

Abstract

Histone methylation status is an important process associated with cell growth, survival, differentiation and gene expression in human diseases. As a member of the KDM4 family, KDM4B specifically targets H1.4K26, H3K9, H3K36, and H4K20, which affects both histone methylation and gene expression. Therefore, KDM4B is often regarded as a key intermediate protein in cellular pathways that plays an important role in growth and development as well as organ differentiation. However, KDM4B is broadly defined as an oncoprotein that plays key roles in processes related to tumorigenesis, including cell proliferation, cell survival, metastasis and so on. In this review, we discuss the diverse roles of KDM4B in contributing to cancer progression and normal developmental processes. Furthermore, we focus on recent studies highlighting the oncogenic functions of KDM4B in various kinds of cancers, which may be a novel therapeutic target for cancer treatment. We also provide a relatively complete report of the progress of research related to KDM4B inhibitors and discuss their potential as therapeutic agents for overcoming cancer.

Whole genome sequencing of Malaysian colorectal cancer patients reveals specific druggable somatic mutations

“…KDM4 proteins family consist of four paralogues, namely KDM4A - KDM4D , and two pseudogenes, KDM4E and KDM4F . While KDM4A and KDM4B are the widely-studied members of the KDM4 subfamily, the roles of KDM4E in cancers have rarely been reported ( Wang et al, 2022a ). Genomic alterations and overexpression of the KDM4 family are reported in different breast cancer subtypes.…”

Target enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy

“…PHGDH is the major rate‐limiting enzyme in the first step of the SGOC pathway, which is abnormal in various diseases, particularly in cancers 30–32 . Intratumor hypoxia is common in cancers, and hypoxia‐inducible factors (HIFs) coordinate the gene expression of PHGDH and its downstream enzymes in the SGOC pathway 33–35 . Hypoxia induces the expression of PHGDH, and PHGDH expression is essential for increasing the availability of reduced GSH to maintain redox homeostasis under hypoxic conditions 36 .…”

“…[30][31][32] Intratumor hypoxia is common in cancers, and hypoxiainducible factors (HIFs) coordinate the gene expression of PHGDH and its downstream enzymes in the SGOC pathway. [33][34][35] Hypoxia induces the expression of PHGDH, and PHGDH expression is essential for increasing the availability of reduced GSH to maintain redox homeostasis under hypoxic conditions. 36 Interestingly, PHGDH also exhibits regulatory potential for cancer stem cells (CSCs).…”

Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells

“…Lipid synthesis is a key nutrient metabolic pathway that allows organisms to remain active even when energy is limited ( Caron et al, 2015 ; Wang et al, 2021 ). Adipogenic differentiation of MSCs is a key developmental process associated with metabolic homeostasis and nutritional signal transduction ( Fernandez-Veledo et al, 2013 ; Lee et al, 2016 ).…”