Last update 01 Nov 2024

KDM3B

Last update 01 Nov 2024

Basic Info

Synonyms

[histone H3]-dimethyl-L-lysine(9) demethylase 3B, C5orf7, chromosome 5 open reading frame 7

+ [12]

Introduction

Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity.

Drugs associated with KDM3B

KA-7

Target

KDM3B

Mechanism

KDM3B agonists

Active Org.-

Originator Org.-

Active Indication

acute leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

P3FI-63

Target

KDM3B

Mechanism

KDM3B inhibitors

Active Org.

National Cancer Institute [+1]

Originator Org.

Leidos, Inc.

Active Indication

Rhabdomyosarcoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

P3FI-90

Target

KDM3B

Mechanism

KDM3B inhibitors

Active Org.

Leidos, Inc. [+1]

Originator Org.

Leidos, Inc.

Active Indication

Rhabdomyosarcoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KDM3B

100 Translational Medicine associated with KDM3B

0 Patents (Medical) associated with KDM3B

Literatures (Medical) associated with KDM3B

04 Oct 2024·Cancer Discovery

CRISPR Dependency Screens in Primary Hematopoietic Stem Cells Identify KDM3B as a Genotype-specific Vulnerability in IDH2- and TET2-mutant Cells

Article

Author: Bagish, Maya ; Wu, Xiaodi ; Wereski, Matthew ; Sango, Junya ; Park, Young C. ; Shih, Alan H. ; Waarts, Michael R. ; Mowla, Shoron ; Cai, Sheng F. ; Miles, Linde A. ; Romero-Vega, Angelica C. ; Fernández-Maestre, Inés ; Csete, Isabelle ; Butler, Jason M. ; Martinez Benitez, Anthony R. ; Eisman, Shira E. ; Bowman, Robert L. ; Boileau, Meaghan ; O’Connor, Kavi ; Koche, Richard P. ; Levine, Ross L. ; Armstrong, Scott A. ; Shan, Yufan ; Papapetrou, Eirini P. ; Xiao, Wenbin

AbstractClonal hematopoiesis (CH) is a common premalignant state in the blood and confers an increased risk of blood cancers and all-cause mortality. Identification of therapeutic targets in CH has been hindered by the lack of an ex vivo platform amenable for studying primary hematopoietic stem and progenitor cells (HSPCs). Here, we utilize an ex vivo co-culture system of HSPCs with bone marrow endothelial cells to perform CRISPR/Cas9 screens in mutant HSPCs. Our data reveal that loss of the histone demethylase family members Kdm3b and Jmjd1c specifically reduces the fitness of Idh2- and Tet2-mutant HSPCs. Kdm3b loss in mutant cells leads to decreased expression of critical cytokine receptors including Mpl, rendering mutant HSPCs preferentially susceptible to inhibition of downstream JAK2 signaling. Our study nominates an epigenetic regulator and an epigenetically regulated receptor signaling pathway as genotype-specific therapeutic targets and provides a scalable platform to identify genetic dependencies in mutant HSPCs.Significance: Given the broad prevalence, comorbidities, and risk of malignant transformation associated with CH, there is an unmet need to identify therapeutic targets. We develop an ex vivo platform to perform CRISPR/Cas9 screens in primary HSPCs. We identify KDM3B and downstream signaling components as genotype-specific dependencies in CH and myeloid malignancies.See related commentary by Khabusheva and Goodell, p. 1768

01 Jul 2024·Archives of Biochemistry and Biophysics

Histone demethylase KDM3B mediates matrix stiffness-induced osteogenic differentiation of adipose-derived stem cells

Article

Author: Zhang, Tao ; Ma, Huangshui

Biomechanical signals in the extracellular niche are considered promising for programming the lineage specification of stem cells. Recent studies have reported that biomechanics, such as the microstructure of nanomaterials, can induce adipose-derived stem cells (ASCs) to differentiate into osteoblasts, mediating gene regulation at the epigenetic level. Therefore, in this study, transcriptome expression levels of histone demethylases in ASCs were screened after treatment with different matrix stiffnesses, and histone lysine demethylase 3B (KDM3B) was found to promote osteogenic differentiation of ASCs in response to matrix stiffness, indicating a positive modulatory effect on this biological process. ASCs exhibited widespread and polygonal shapes with a distinct bundle-like expression of vinculin parallel to the axial cytoskeleton along the cell margins on the stiff matrix rather than round shapes with a smeared and shorter expression on the soft matrix. Comparatively rigid polydimethylsiloxane material directed ASCs into an osteogenic phenotype in inductive culture media via the upregulation of osteocalcin, alkaline phosphatase, and runt-related transcription factor 2. Treatment with KDM3B-siRNA decreased the expression of osteogenic differentiation markers and impaired mitochondrial dynamics and mitochondrial membrane potential. These results illustrate the critical role of KDM3B in the biomechanics-induced osteogenic commitment of ASCs and provide new avenues for the further application of stem cells as potential therapeutics for bone regeneration.

01 May 2024·International Journal of Radiation Oncology*Biology*Physics

KDM3B Single-Nucleotide Polymorphisms Impact Radiation Therapy Toxicity Through Circular RNA-Mediated KDM3B Expression and Inflammatory Responses

Article

Author: Sun, Yin ; Kerns, Sarah ; Zhou, Zhen ; Chen, Jinbo ; Tsai, Ying ; Shen, Binghui ; Zeng, Guohua ; Chen, Yuhchyau ; Wood, Ronald ; Marples, Brian

PURPOSEGenome-wide association studies have identified single-nucleotide polymorphisms (SNPs) associated with radiation therapy (RT) toxicities in patients with prostate cancer. SNP rs17599026 in intron 21 of KDM3B is significantly associated with the development of late urinary toxicity, specifically in the increase in urinary frequency 2 years after RT compared with pretreatment conditions. The present study aimed to provide mechanistic insights for this association.METHODS AND MATERIALSUsing human tissues and cell lines, we examined the protein expression of KDM3B and molecular mechanisms underlying the SNP modulation by variants of KDM3B SNP alleles. In animals with normal and heterozygous expressions of Kdm3b, we examined the relationship between Kdm3b expression and radiation toxicity.RESULTSKDM3B rs17599026 lies in a motif important for circular RNA expression that is responsible for sponging miRNAs to regulate KDM3B expression. Using a murine model with heterozygous deletion of the Kdm3b gene, we found that lower Kdm3b expression is associated with altered pattern of urination after bladder irradiation, which is related to differential degrees of tissue inflammation as measured by analyses of gene expression, lymphocyte infiltration, and noninvasive ultrasound imaging.CONCLUSIONSKDM3B SNPs can impact its expression through regulating noncoding RNA expression. Differential KDM3B expression underlies radiation toxicity through tissue inflammation at the molecular and physiological level. Our study outcome offers a foundation for mechanism-based mitigation for radiation toxicity for prostate cancer survivors.

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KDM3B

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