Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 77-89 http://medscipublisher.com/index.php/cge 80 because changes in these two markers can cause significant variations in gene activity and cell characteristics (Popovic et al., 2014; Laliotis and Lin, 2022). 3.2 Dysmethylation in prostate cancer: its role in progression The imbalance of histone methylation is an important feature of the deterioration of prostate cancer. Abnormal expression of histone methyltransferases and demethylases can cause the genes that manage cell proliferation, death and spread to be wrongly turned on or off. For instance, the elevated expression of EZH2, which promotes the trimethylation of H3K27, has been found in anti-castrating prostate cancer (CRPC) and is associated with adverse consequences. Similarly, overexpression of NSD2 is also associated with the characteristics of invasive prostate cancer and a shorter disease-free survival time (Filon et al., 2021). NSD2 is responsible for the methylation of H3K36. The mutual influence among different histone markers is also crucial in prostate cancer. For instance, excessive expression of MMSET/NSD2 in multiple myeloma can lead to an overall increase in H3K36me2 and a decrease in H3K27me3, indicating a wa-or-fall relationship among these changes (Popovic et al., 2014). This imbalance can activate oncogenes and turn off tumor suppressor genes, thereby promoting the progression of cancer. In addition, histone modification enzyme mutations that affect H3K27 and H3K36 have been proven to be prognostic markers for various cancers, including prostate cancer (Laliotis and Lin, 2022). 3.3 Therapeutic significance: targeting methyltransferase and demethylase Targeting histone methyltransferases and demethylases is a promising approach for the treatment of prostate cancer. EZH2 inhibitors, such as tazemetostat, have shown effectiveness in animal studies and are currently being tested on patients with various cancers, including prostate cancer (Laugesen et al., 2019). These drugs work by preventing EZH2 from adding methyl groups, thereby reducing the trimethylation level of H3K27 and reactivating dormant tumor suppressor genes. Targeting NSD2 and other H3K36 methyltransferases may also bring therapeutic benefits. Drugs that block NSD2 from reaching the target or directly suppress its enzymatic activity are under development and have shown promise in animal experiments (Popovic et al., 2014). In addition, natural components such as green tea extract and curcumin have been found to affect the activities of histone methyltransferase and demethylase, providing supplementary options for conventional therapies (Dorna et al., 2023). 4 The Role of Histone Acetylation in Prostate Cancer 4.1 The role of acetylation in chromatin structure and gene expression Histone acetylation is an important chemical modification that can affect chromatin structure and gene expression. This modification mainly occurs on the lysine of histones. It can neutralize the positive charge of histones and weaken the attraction between histones and negatively charged DNA. In this way, the chromatin structure becomes looser, and transcription factors and RNA polymerase can bind more easily, thereby promoting gene transcription (Figure 2) (Li et al., 2020). On the contrary, if deacetylation occurs, chromatin will become compact and gene transcription will also be inhibited. The acetylation and deacetylation of histones maintain a dynamic balance, which is crucial for regulating gene expression, and this balance is strictly controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs) (Schizas et al., 2019). Li et al. (2020) found that acetylation and deacetylation play a key role in the regulation of gene expression. Acetylation opens up the chromatin structure, which is conducive to gene transcription. HDAC tighens chromatin through deacetylation and inhibits gene expression. HDAC inhibitors (HDACi) can inhibit the activity of HDAC, restore chromatin to a loose state, and thereby promote the expression of important tumor suppressor genes. In cancer treatment, HDACi is expected to prevent the growth and division of cancer cells through this mechanism. 4.2 Histone acetyltransferases and histone deacetylases During the occurrence and development of prostate cancer, the dysfunction of HATs and HDACs plays a promoting role. Especially HDACs, which are often overexpressed in prostate cancer cells, lead to abnormal
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