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Updated: May 15, 2026
Direct Measurement of KDM1A Target Engagement Using Chemoprobe-based Immunoassays
Published on: June 13, 2019
KDM1 is a novel therapeutic target for the treatment of gliomas
Gangadhara R Sareddy1, Binoj C Nair, Samaya K Krishnan
1The Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Sareddy@uthscsa.edu
Abstract:
Glioma development is a multistep process, involving alterations in genetic and epigenetic mechanisms. Understanding the mechanisms and enzymes that promote epigenetic changes in gliomas are urgently needed to identify novel therapeutic targets. We examined the role of histone demethylase KDM1 in glioma progression. KDM1 was overexpressed in gliomas and its expression positively correlated with histological malignancy. Knockdown of KDM1 expression or its pharmacological inhibition using pargyline or NCL-1 significantly reduced the proliferation of glioma cells. Inhibition of KDM1 promoted up regulation of the p53 target genes p21 and PUMA. Patient-derived primary GBM cells expressed high levels of KDM1 and pharmacological inhibition of KDM1 decreased their proliferation. Further, KDM1 inhibition reduced the expression of stemness markers CD133 and nestin in GBM cells. Mouse xenograft assays revealed that inhibition of KDM1 significantly reduced glioma xenograft tumor growth. Inhibition of KDM1 increased levels of H3K4-me2 and H3K9-Ac histone modifications, reduced H3K9-me2 modification and promoted expression of p53 target genes (p21 and PUMA), leading to apoptosis of glioma xenograft tumors. Our results suggest that KDM1 is overexpressed in gliomas and could be a potential therapeutic target for the treatment of gliomas.
Insights
Histone demethylase KDM1 is overexpressed in gliomas, promoting tumor progression. Inhibiting KDM1 reduces glioma cell proliferation and tumor growth, offering a potential therapeutic strategy for glioma treatment.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Glioma development involves complex genetic and epigenetic alterations.
- Understanding epigenetic modifiers in gliomas is crucial for identifying therapeutic targets.
Purpose of the Study:
- To investigate the role of histone demethylase KDM1 in glioma progression.
- To evaluate KDM1 as a potential therapeutic target for glioma treatment.
Main Methods:
- Examined KDM1 expression in gliomas.
- Utilized KDM1 knockdown and pharmacological inhibitors (pargyline, NCL-1).
- Assessed effects on glioma cell proliferation, stemness markers, and tumor growth in mouse xenografts.
Main Results:
- KDM1 was overexpressed in gliomas, correlating with malignancy.
- KDM1 inhibition reduced glioma cell proliferation and stemness markers (CD133, nestin).
- Inhibition decreased tumor growth in vivo, increasing apoptosis via p53 target genes (p21, PUMA).
Conclusions:
- KDM1 is a key driver of glioma progression and a promising therapeutic target.
- Targeting KDM1 offers a novel strategy for glioma treatment.
