Mechanism of LncRNA CBR3-AS1 in regulating pyroptosis of intestinal epithelial cells in ulcerative colitis.

Ulcerative colitis (UC) is a common chronic relapsing inflammatory disease that threatens human life. This study aims to explore the mechanism of LncRNA CBR3-AS1 in pyroptosis of intestinal epithelial cells in UC. The levels of CBR3-AS1, KLF2, and SUGT1 in UC cells were detected. After downregulating CBR3-AS1 expression, cell viability and pyroptosis were measured, followed by the detection of SOD and MDA levels. The binding of CBR3-AS1 to EZH2, enrichment of EZH2 and H3K27me3 on the KLF2 promoter, and binding of KLF2 to the SUGT1 promoter were assayed. The role of CBR3-AS1 in pyroptosis was validated in animal models. We found that CBR3-AS1 and SUGT1 were increased in UC cells, and KLF2 was decreased. After downregulation of CBR3-AS1, cell viability was increased and pyroptosis was alleviated. CBR3-AS1 recruited EZH2 to occupy the KLF2 promoter, leading to increased H3K27me3 levels and suppressed KLF2 expression, reducing the enrichment of KLF2 on the SUGT1 promoter, finally promoting SUGT1 expression. SUGT1 overexpression or KLF2 downregulation alleviated the protective effect of silencing CBR3-AS1 on pyroptosis in UC cells. CBR3-AS1 downregulation alleviates cell pyroptosis in colonic tissues. In conclusion, CBR3-AS1 exacerbated pyroptosis of intestinal epithelial cells in UC via the KLF2/SUGT1 pathway.