Oncogenic super-enhancer formation in tumorigenesis and its molecular mechanisms

Super-enhancers (SEs) consist of a cluster of many enhancers bound to a great number of transcription factors. They are critical cis-regulatory elements that determine the identity of various human cell types. During tumorigenesis, DNA mutations and indels, chromosomal rearrangements, three-dimensional chromatin structural changes, and viral infections mediate oncogenic SE activation, and activated SEs have been found to regulate the expression of oncogenic genes. Inhibition specifically targeted to oncogenic SE assembly and activation provides a novel powerful therapeutic strategy for various cancers. In this paper, we first introduce the current understanding of oncogenic SE assembly and activation and then summarize the pathogenic factors and mechanism of oncogenic SE activation. Next, we elaborate on the oncogenic functions of SEs in cancers and the application of SEs as therapeutic targets. Finally, we turn our focus to the use of SEs in basic research and clinical trials. Cancer: Enhancing the expression of cancer-causing genes Drugs that block the assembly and activation of large DNA segments involved in enhancing gene expression could help in the treatment of cancer. Faqing Tang of Hunan Cancer Hospital in Changsha, China, and colleagues review the ways in which cancer cells hijack clusters of gene-regulating sequences known as super-enhancers, regulatory gene regions that normally help determine a cell's unique identity, to drive the aberrant gene activity that fuels tumor growth. The researchers describe how numerous factors, ranging from internal DNA alterations, both large and small, to viral infections and other external assaults, can spur the formation of cancer-causing super-enhancers, leading to out-of-control gene expression. Therapies that selectively target these super-enhancers are now in early clinical testing. However, more studies of super-enhancers and their role in cancer development are needed to inform future drug development.