Epigenomics, Transcriptomics, and Translational Control in Prostate Cancer

Epigenetics refers to changes in gene expression that are not caused by changes in the underlying DNA sequence. It is now clear that epigenetic changes may play a significant role in prostate cancer (PC) development and progression and can also be used to personalize treatment for PC patients. DNA methylation involves the addition of a methyl group to a cytosine or adenine base in the DNA molecule, which can lead to changes in gene expression. CpG dinucleotides are found in clusters called CpG islands, which are commonly found in promoter regions of genes. DNA methylation in promoter regions is associated with gene silencing, as it blocks the binding of transcription factors and RNA polymerase. Histone modifications, such as acetylation, can also influence gene expression by altering the accessibility of DNA to transcription factors and other regulatory proteins. Regulation of gene transcription is one of many antagonistic roles linked to H2A.Z nucleosome, and its overexpression has been associated with poor prognosis and increased metastasis. Among various histone modifications, H3K9, H3K18, H3K27, and H4K12 have been the focus of extensive research. A number of miRNA dysregulations have been identified in PC, and these dysregulated miRNAs have been implicated in the regulation of key pathways involved in cell proliferation, apoptosis, angiogenesis, and tumor metastasis.