Remodeling characteristics of super-enhancers in intestinal gastric cancer and their roles in upregulating CEMIP expression

Objective‍ ‍To map the super-enhancers remodeling of intestinal gastric cancer and reveal the tumor biological functions of the super-enhancers and the downstream target genes that may be activated. Methods‍ ‍A total of 31 normal gastric mucosal tissues， 23 intestinal gastric cancer tissues and 9 intestinal gastric cancer organoids were collected from the Department of Gastroenterology of Army Medical Center of PLA from January to December 2022. Chromatin targeting histone H3K27ac modified chromatin targeting cleavage under targets and tagmentation （CUT&Tag） sequencing was conducted on above tissues. The remodeling profiles of super-enhancers in intestinal gastric cancer were analyzed and the key target genes were identified based on bioinformation tools. CRISPRi technology was used to intervene with the super-enhancers， the expression of target genes was detected with Western blotting， and the proliferation， migration and invasion abilities were detected by CCK-8 assay and Transwell chambers in the control group and the intervention group. Results‍ ‍There was a significant difference in the signal of super-enhancers between intestinal gastric cancer tissues and normal gastric mucosal tissues （P<0.05）， and the active super-enhancers in cancer tissues may be involved in biological processes such as negative regulation of the immune system and cell adhesion. The expression of up-regulated cell migration-inducing protein （CEMIP） in tumor cells was regulated by the super-enhancers， and intervening the super-enhancers down-regulated the expression of CEMIP （P<0.05）， and inhibited the cell proliferation， invasion and migration abilities of tumor cells （P<0.05）. Conclusion‍ ‍Super-enhancer remodeling is observed in intestinal gastric cancer， and they can up-regulate the expression of CEMIP gene and promote the growth， migration and invasion of cancer cells.