The role of super-enhancer-driven lncRNAs in cancer

In recent years, the global burden of cancer has grown substantially, yet available treatments and clinical outcomes remain inadequate. Accordingly, research into novel therapeutic targets for cancer has become a major focus. Super-enhancers (SEs), which are clusters of multiple enhancers, represent essential epigenetic oncogenic factors that are critical for maintaining cancer cell identity. Moreover, SE-driven long non-coding RNAs (lncRNAs) play a crucial regulatory role in tumor initiation and progression. Targeting cancer-specific SE-driven lncRNAs can slow tumor development and offer a novel strategy for cancer treatment. This review first outlines the characteristics of SEs, including their relevance to phase separation (PS) and the core transcriptional regulatory circuitry (CRC). It then describes the fundamental characteristics, intracellular localization, and functions of SE-driven lncRNAs, with emphasis on the analytical methods for these lncRNAs and their roles in tumors. Finally, the review highlights the clinical applications of existing SE inhibitors in oncology and their potential for targeting SE-driven lncRNAs, aiming to advance translational research in this field.