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The most cutting-edge research has revealed that membrane-less organelles, such as the nucleolus, stress granule, processing body, and nuclear speckles form subcellular compartments to facilitate signaling transduction and transcriptional regulation by liquid–liquid phase separation 23, 24, 25. On the other hand, this addiction makes SEs and SE-related genes as potential therapeutic targets and diagnosis 22. It is worth noting that the expression level of SE-related genes is significantly higher than that of the typical enhancer-control genes, which has been widely validated in a variety of cancer types 21. As shown in mESCs, pluripotency genes like OCT4, SOX2, and NANOG are all controlled and activated by SEs, given the concept that SEs can drive specific gene expression that controls and defines the cell identity and engages in cell-type-specific biological processes 20. Generally accepted models of SEs are considered to be large clusters of regulatory elements (after over 20 Kb) binding with dense transcriptional coactivators, such as BRD4 and CDK7, and with high potential to activate target gene expression output 19 (summarized in Table 1). The ROSE (Rank ordering of super-enhancers) algorithm is designed to search SEs by locating genomic proximity for grouping elements to a putative target gene 17, 18. The SE was first proposed in mouse embryonic stem cells (mESCs), by chromatin immunoprecipitation (ChIP)-sequencing analysis of active histone marker (H3K27ac) and other TFs 17. Then the basal machinery is recruited to initiate the downstream transcription activity (depicted in Fig. Specific TFs bind to SE to trigger promoter-enhancer interaction, mediated by chromatin looping, to load the SE to the cognate promoter. Similar to the typic enhancer, SE incorporates modelized regulation mechanisms. Super-enhancer (SE) is defined as large clusters of enhancers spanning across a long-range region of genomic DNA that drives stronger transcriptional activation ability than individual enhancers 4. ![]() 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. 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. #EL P CANCER FOR CURE RAR 320 AREA DRIVERS#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. One of the most important epigenetic alternations is the non-coding regulatory element, which includes both enhancers and super-enhancers (SEs). Genetic and epigenetic alterations may mediate dysregulated transcriptional activity. ![]() Transcriptional dysregulation of these pathways is commonly associated with tumorigenesis and the development of cancer. Abnormal activity of oncogenic and tumor-suppressor signaling pathways contributes to cancer and cancer risk in humans. ![]() ![]()
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