Table 1.
The function of histone acetyltransferases & histone deacetylases in GBM.
| Enzyme | Associated role in GBM | Cell lines/model system used | References |
|---|---|---|---|
| KAT6A | Promotion of H3K23 acetylation through interaction with TRIM24, leading to PI3K/AKT pathway upregulation | U87, LN229 | (50) |
| HDAC1 | Elevated expression in GBM; increased apoptosis, decreased cellular migration, and decreased MAPK signaling upon knockdown in vitro | Patient-derived cell cultures (52); U251, T98G (53); U87 (54) | (51–55) |
| HDAC3 | Overexpression associated with decreased overall survival; inhibition leads to increased TMZ-induced cell death | (51, 56) | |
| HDAC4 | Overexpression associated with increased cell proliferation/invasiveness and decreased ROS production, knockdown associated with p21WAF/Cip1-mediated radiation-induced senescence and decreased stem marker expression | U87, U251 | (55, 57–59) |
| HDAC6 | Conflicting associations between expression in tumors and overall survival, knockdown impairs EGFR pathway and increases apoptosis and autophagy in vitro | U87, U251 | (51, 59, 60) |
| HDAC9 | Knockdown leads to reduced proliferation and downregulation of EGFR signaling pathway | U87 | (61) |
| SIRT1 | Selective inhibition leads to apoptosis in engineered NSCs and GSCs but not U87 cells, and reduced expression of stem markers in GSCs | U87, engineered NSCs, GSCs | (62) |
| SIRT1 | Conflicting evidence – research on primary tumor tissue showed decreased protein expression and that overexpression in GBM cell lines suppressed cell growth, while contrasting research showed SIRT2 essentiality in mediating decreased cellular proliferation in GSCs upon treatment with resveratrol | Glioma cell lines (unspecified), GSCs, NSCs | (63, 64) |
| SIRT3 | Overexpressed in GSCs, interacts with TRAP1 to activate SOD2 and prevent ROS overproduction. Knockdown leads to increased ROS production and loss of stemness | GSCs | (65) |
| SIRT6 | Overexpression leads to apoptosis and JAK-STAT pathway downregulation in vitro, conflicting evidence about expression in GBM | T98G | (51, 66–68) |
A summary of the functions of individual histone deacetylase and acetyltransferase enzymes in GBM pathophysiology, and the corresponding model system(s) used and reference to the original publication(s).