Super-enhancer in prostate cancer: transcriptional disorders and therapeutic targets

Abstract

Abnormal activity of oncogenic and tumor-suppressor signaling pathways contributes to cancer and cancer risk in humans. Transcriptional dysregulation of these pathways is commonly associated with tumorigenesis and the development of cancer. Genetic and epigenetic alterations may mediate dysregulated transcriptional activity. One of the most important epigenetic alternations is the non-coding regulatory element, which includes both enhancers and super-enhancers (SEs). SEs, characterized as large clusters of enhancers with aberrant high levels of transcription factor binding, have been considered as key drivers of gene expression in controlling and maintaining cancer cell identity. In cancer cells, oncogenes acquire SEs and the cancer phenotype relies on these abnormal transcription programs driven by SEs, which leads to cancer cells often becoming addicted to the SEs-related transcription programs, including prostate cancer. Here, we summarize recent findings of SEs and SEs-related gene regulation in prostate cancer and review the potential pharmacological inhibitors in basic research and clinical trials.

Fig. 1. The structure and function of enhancer and super-enhancer.

a Schematic structure of the typical enhancer. b Schematic structure of the super-enhancer. H3K27ac, acetylation of histone 3 lysine 27; TF, transcription factor; RNA pol II, RNA polymerase II; mRNA, messenger RNA.

Fig. 2. Schematic illustration of super-enhancer-mediated action in prostate cancer.

Proposed mode of the mechanism of super-enhancer-mediated action in prostate cancer. H3K27ac, acetylation of histone 3 lysine 27; AR, androgen receptor; BRD2/3/4, bromodomain containing protein 2/3/4; CDK7, cyclin dependent kinase 7; CDK9, cyclin dependent kinase 9; ERG, erythroblast transformation-specific-related gene; MED1, mediator complex subunit 1; RNA pol II, RNA polymerase II.