TY - JOUR
T1 - The role of histone H3 lysine demethylases in glioblastoma
AU - Young, Dejauwne
AU - Guha, Chandan
AU - Sidoli, Simone
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Glioblastoma
KW - Histone methylation
KW - Lysine demethylases
KW - Post-translational modifications
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U2 - 10.1007/s10555-023-10114-1
DO - 10.1007/s10555-023-10114-1
M3 - Review article
C2 - 37286866
AN - SCOPUS:85161319522
SN - 0167-7659
VL - 42
SP - 445
EP - 454
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 2
ER -