Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 77-89 http://medscipublisher.com/index.php/cge 79 Figure 1 Feedback loop and histone modifications involved in the accumulation of the chromosomal passenger complex (CPC) at centromeres (Adapted from Schmitz et al., 2020) Image caption: a: After Bub1 kinase phosphorylates H2AT120, it is recognized by Sgo1; CPC is recruited to the pericentromere through the interaction between Borealin and Sgo1 and is guided to the centromere by direct binding of Survivin to H3T3ph; Aurora B phosphorylates Haspin to enhance its kinase activity, thereby increasing the accumulation of H3T3ph and CPC at the centromere; b: Repo-Man, through its binding with PP1γ, removes H3T3ph from chromosome arms during prophase, while Aurora B protects centromeric H3T3ph from being dephosphorylated; Aurora B inhibits the interaction between Repo-Man, PP1γ, and histones through phosphorylation (Adapted from Schmitz et al., 2020) In cancer, the imbalance of histone modification is a common cause of abnormal gene expression and tumor development. Abnormal histone modifications can activate oncogenes or disable tumor suppressor genes, thereby promoting the growth and survival of cancer cells. For instance, the misregulation of histone methylation and acetylation is associated with a variety of cancers, including prostate cancer. These alterations can affect the expression of genes that control cell division, programmed death, and spread and metastasis. Understanding the specific role of histone modification in cancer can help discover potential therapeutic targets (Huang et al., 2015; Balaji et al., 2022). 3 The role of Histone Methylation in Prostate Cancer 3.1 Histone methylation mechanisms: H3K4, H3K9, H3K27, H3K36 Histone methylation is a key epigenetic change that regulates the nuclear structure and thereby controls gene activity. Specific lysine sites on histone H3, such as H3K4, H3K9, H3K27 and H3K36, are the main locations where methylation occurs, and each site is associated with different regulatory effects. The methylation of H3K4 is mainly driven by the KMT2 (MLL) protein family and is usually linked to the active transcription of genes. Multiple enzymes such as SMYD and SET7/9 are also involved in H3K4 methylation, affecting histone and non-histone targets (Yang et al., 2021). On the contrary, H3K9 methylation is generally associated with gene closure and the formation of dense chromatin regions. The enzymes that catalyze the methylation of H3K9 are SUV39H1 and G9a, which play a role in maintaining genomic stability and silencing repetitive DNA fragments (Tian et al., 2013). H3K27 methylation catalyzed by the multi-comb inhibitory complex 2 (PRC2) is crucial for shutting down genes and is involved in the development process and cancer deterioration. EZH2 is the core part of PRC2. It can cause H3K27 to carry three methyl groups, resulting in the cessation of transcription (Laugesen et al., 2019). The methylation of H3K36 driven by enzymes such as SETD2 and NSD2 is related to the extension of gene transcription and RNA splicing. The balance between methylation of H3K36 and H3K27 is particularly important
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