Epigenetic modifications in prostate cancer
Masahiro Sugiura1,2, Hiroaki Sato1,2, Manato Kanesaka1,2
1Departments of, Department of, Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Abstract:
Prostate cancer is a major cause of cancer-related deaths among men worldwide. In addition to genomic alterations, epigenetic alterations accumulated in prostate cancer have been elucidated. While aberrant deoxyribonucleic acid hypermethylation in promoter CpG islands inactivates crucial genes associated with deoxyribonucleic acid repair, cell cycle, apoptosis or cell adhesion, aberrant deoxyribonucleic acid hypomethylation can lead to oncogene activation. Acetylation of histone is also deregulated in prostate cancer, which could cause aberrant super-enhancer formation and activation of genes associated with cancer development. Deregulations of histone methylation, such as an increase of trimethylation at position 27 of histone H3 by enhancer of zeste homolog2 overexpression, or other modifications, such as phosphorylation and ubiquitination, are also involved in prostate cancer development, and inhibitors targeting these epigenomic aberrations might be novel therapeutic strategies. In this review, we provide an overview of epigenetic alterations in the development and progression of prostate cancer, focusing on deoxyribonucleic acid methylation and histone modifications.
Insights
Epigenetic alterations, including DNA methylation and histone modifications, are key drivers in prostate cancer development and progression. Targeting these epigenomic changes offers potential novel therapeutic strategies for this widespread cancer.
Area of Science:
- Oncology
- Epigenetics
Background:
- Prostate cancer is a leading cause of cancer death in men globally.
- Epigenetic alterations, including DNA methylation and histone modifications, play a significant role in prostate cancer development alongside genomic changes.
Purpose of the Study:
- To provide a comprehensive overview of epigenetic alterations in prostate cancer.
- To focus on the roles of DNA methylation and histone modifications in prostate cancer development and progression.
Main Methods:
- Review of existing literature on epigenetic alterations in prostate cancer.
- Analysis of the impact of DNA methylation (hyper- and hypomethylation) and histone modifications (acetylation, methylation, phosphorylation, ubiquitination) on gene expression and cancer development.
Main Results:
- Aberrant DNA hypermethylation inactivates tumor suppressor genes involved in DNA repair, cell cycle, apoptosis, and cell adhesion.
- Aberrant DNA hypomethylation can lead to oncogene activation.
- Histone acetylation deregulation contributes to aberrant super-enhancer formation and gene activation.
- Histone methylation (e.g., H3K27 trimethylation via EZH2) and other modifications are implicated in prostate cancer.
Conclusions:
- Epigenetic aberrations are crucial in prostate cancer pathogenesis.
- Targeting these epigenomic alterations presents promising avenues for novel therapeutic strategies.
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