Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 77-89 http://medscipublisher.com/index.php/cge 77 Research Insights Open Access Role of Histone Modifications in Prostate Cancer Liqin Guo, Jiayi Wu Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: jiayi.wu@cuixi.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.2 doi: 10.5376/cge.2025.13.0008 Received: 09 Feb., 2025 Accepted: 13 Mar., 2025 Published: 26 Mar., 2025 Copyright © 2025 Guo and Wu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Guo L.Q., and Wu J.Y., 2025, Role of histone modifications in prostate cancer, Cancer Genetics and Epigenetics, 13(2): 77-89 (doi: 10.5376/cge.2025.13.0008) Abstract This study analyzed the role of histone modification in prostate cancer, with a focus on exploring histone methylation, acetylation, and how their associations affect cancer development. This study explored how these modifications cause cancer cells to develop drug resistance and also evaluated therapeutic approaches targeting histone modifications. Abnormal changes in histone modifications, especially methylation and acetylation, are key factors in the pathogenesis, deterioration and development of treatment resistance of prostate cancer. The interaction among histone modifications has a significant impact on the internal structure of the cell nucleus and gene activity. Drugs targeting these modifications, such as HDAC inhibitors and methyltransferase inhibitors, have shown promising prospects in the treatment of prostate cancer. Understanding the specific process of histone modification is crucial for improving the therapeutic effect of prostate cancer, especially in addressing cancer development and treatment drug resistance. Epigenetic therapy targeting histone modification may offer new treatment options for prostate cancer patients, provide a foundation for personalized treatment, help identify new biomarkers and therapeutic targets, and promote the development of prostate cancer treatment. Keywords Prostate cancer; Histone modification; Methylation; Acetylation; Epigenetic therapy 1 Introduction Prostate cancer is one of the most common malignant tumors among men worldwide and is also one of the main causes of cancer-related deaths among men (Jeronimo et al., 2011; Nowacka-Zawisza and Wiśnik 2017; Sugiura et al., 2020). There are many causes of this disease, which are related to genetic factors and living environment. Although there have been advancements in the early detection and treatment of prostate cancer nowadays, it remains a serious health problem because of its complex biological characteristics and its tendency to develop into more difficult-to-deal types (Dobosy et al., 2007). Prostate cancer often progresses from local symptoms to metastatic castration-resistant prostate cancer. This situation is difficult to treat and the recovery of patients is not good (Chin et al., 2011). Epigenetics studies heritable changes in gene expression that do not alter the sequence of DNA. These changes include DNA methylation, histone modification, and the regulation of non-coding Rnas such as micrornas (mirnas) (Li et al., 2005; Jeronimo et al., 2011; Nowacka-Zawisza and Wiśnik 2017; Mason, 2024). During the development of cancer, epigenetic mechanisms play a key role by regulating the gene expression patterns that control cell growth, differentiation and death (Jeronimo et al., 2011; Burlibașa et al., 2023). Unlike gene mutations, epigenetic changes can be reversed, which makes it an important breakthrough in cancer treatment (Li et al., 2005; Dobosy et al., 2007). Histone modifications, such as acetylation, methylation, phosphorylation and ubiquitination, play important regulatory roles in chromatin structure and gene expression (Seligson et al., 2005; Jeronimo et al., 2011; Sugiura et al., 2020). In patients with prostate cancer, abnormal histone modification can lead to dysfunctions of genes related to tumor formation and cancer development (Ellinger et al., 2010; Baumgart and Haendler, 2017). For instance, when zeste homologous enhancer 2 (EZH2) is overexpressed, the trimethylation level of histone H3-lysine 27 (H3K27me3) increases, which is associated with the occurrence of prostate cancer. Furthermore, the overall situation of histone modification can also be used to predict the disease condition, such as whether cancer
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