global-level-quantification-histone-post-translational-modifications

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue

Flat cultures of mammalian cells are a widely used in vitro approach for understanding cell physiology, but this system is limited in modeling solid ...

semi-automated-phenotypic-analysis-functional-3d-spheroid-cell

Semi-Automated Phenotypic Analysis of Functional 3D Spheroid Cell Cultures

We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell ...

Albert Einstein College of Medicine

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with an average survival of 15-18 months. Part of its malignancy derives from epigenetic regulation that occurs as the tumor develops and after therapeutic treatment. Specifically, enzymes involved in removing methylations from histone proteins on chromatin, i.e., lysine demethylases (KDMs), have a significant impact on GBM biology and reoccurrence. This knowledge has paved the way to considering KDMs as potential targets for GBM treatment. For example, increases in trimethylation of histone H3 on the lysine 9 residue (H3K9me3) via inhibition of KDM4C and KDM7A has been shown to lead to cell death in Glioblastoma initiating cells. KDM6 has been shown to drive Glioma resistance to receptor tyrosine kinase inhibitors and its inhibition decreases tumor resistance. In addition, increased expression of the histone methyltransferase MLL4 and UTX histone demethylase are associated with prolonged survival in a subset of GBM patients, potentially by regulating histone methylation on the promoter of the mgmt gene. Thus, the complexity of how histone modifiers contribute to glioblastoma pathology and disease progression is yet to be fully understood. To date, most of the current work on histone modifying enzymes in GBM are centered upon histone H3 demethylase enzymes. In this mini-review, we summarize the current knowledge on the role of histone H3 demethylase enzymes in Glioblastoma tumor biology and therapy resistance. The objective of this work is to highlight the current and future potential areas of research for GBM epigenetics therapy.

ArticleTotal : 2	Year
Publication title Cited by 7	2022
Publication title Cited by 2	2023

Dejauwne Young

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