1. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410007, PR China.
2. Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410007, PR China.
3. Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
4. Hunan key laboratory of the research and development of novel pharmaceutical preparations, Changsha Medical University, Changsha, 410219, PR China.
5. Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha 410011, PR China.
6. Department of Colorectal and Anal Surgery, Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha 410007, PR China.
*These authors contributed equally to this work.
Digestive system tumors include malignancies of the stomach, pancreas, colon, rectum, and the esophagus, and are associated with high morbidity and mortality. Aberrant epigenetic modifications play a vital role in the progression of digestive system tumors. The aberrant transcription of key oncogenes is driven by super-enhancers (SEs), which are characterized by large clusters of enhancers with significantly high density of transcription factors, cofactors, and epigenetic modulatory proteins. The SEs consist of critical epigenetic regulatory elements, which modulate the biological characteristics of digestive system tumors including tumor cell identity and differentiation, tumorigenesis, environmental response, immune response, and chemotherapeutic resistance. The core transcription regulatory loop of the digestive system tumors is complex and a high density of transcription regulatory complexes in the SEs and the crosstalk between SEs and the noncoding RNAs. In this review, we summarized the known characteristics and functions of the SEs in the digestive system tumors. Furthermore, we discuss the oncogenic roles and regulatory mechanisms of SEs in the digestive system tumors. We highlight the role of SE-driven genes, enhancer RNAs (eRNAs), lncRNAs, and miRNAs in the digestive system tumor growth and progression. Finally, we discuss clinical significance of the CRISPR-Cas9 gene editing system and inhibitors of SE-related proteins such as BET and CDK7 as potential cancer therapeutics.
Keywords: digestive system tumors, super-enhancer, tumor progression, non-coding RNAs, therapeutic targets.