TABLE 3.
Functional outcomes of H3 methylation master regulators considered as potential therapeutic targets and biomarkers in BCa.
| Enzyme type | Enzyme name | PTMs | Function in bladder cancer | References |
|---|---|---|---|---|
| HMTs | SMYD3 | H3K4me2/3 | Promotes cell proliferation | Wu et al. (2019) |
| WDR5 | H3K4me1 | Promotes tumor development and proliferation; correlated with advanced tumor stage MBIC and poor survival; decrease in H3K4me1 is correlated with poor prognosis. | Chen et al. (2015) | |
| KMT2C (MLL3) | H3K4me3 | Causes impairments in DNA replication and repair; increased chromatin instability; potential biomarker for high grade NMIBC, and luminal papillary and basal squamous MIBC subtypes. | Rampias et al. (2019) | |
| Martinez et al. (2019) | ||||
| KMT2D (MLL4) | H3K4me1/2 | Causes disorders in DNA replication and cell cycle; induced invasion, and migration; recurrence and resistance to therapy | Sun et al. (2019) | |
| Meghani et al. (2022) | ||||
| G9a | H3K9me2 | Contributes to the development of NMIBC; possesses immunomodulatory effects | Tachibana et al. (2008) | |
| Mourits et al. (2021) | ||||
| EZH2 | H3K27me2/3 | Promotes tumor development and progression in BCa; predicts progression and recurrence in NMIBC | Santos et al. (2014) | |
| Chen et al. (2019) | ||||
| NSD1 | H3K36me2 | Contributes to tumorigenesis | Nakshatri et al. (2015) | |
| KDMs | LSD1 | H3K4me1/2/3 | Promotes cancer development and proliferation | Lan et al. (2013) |
| KDM3A | H3K27me3 | Promotes tumor progression | Wan et al. (2017) | |
| JMJD2A (KDM2A) | H3K9me3 H3K36me3 | Promotes higher-grade BCa | Lu et al. (2022) | |
| KDM6A | H3K27me3 | Induces tumor immune escape; activates proinflammatory pathway; induces deregulation in the expression of cell identity related genes. | Kobatake et al. (2020) | |
| Chen et al. (2021) |