Aims: Few circRNAs have been thoroughly explored in ulcerative colitis (UC). Materials & methods: Microarrays and qualitative real-time PCRs were used to detect and confirm dysregulated circRNAs associated with UC. Functional analysis was performed to explore the roles. Results: A total of 580 circRNAs and 87 miRNAs were simultaneously dysregulated in both inflamed and noninflamed UC colonic mucosa compared with healthy controls. Accordingly, hsa_circ_0001021 was significantly downregulated in patients with UC and was related to Mayo scores. Clinical samples and cell experiments revealed that hsa_circ_0001021 was expressed in epithelial cells and correlated with ZO-1, occludin and CLDN-2. Moreover, hsa_circ_0001021 sponged miR-224-5p to upregulate smad4 and increased ZO-1 and occludin. Conclusion: Hsa_circ_0001021 is related to UC severity and regulates epithelial barrier function via sponging miR-224-5p.
Keywords: hsa_circ_0001021; intestinal epithelial barrier; miR-224-5p; smad4; ulcerative colitis.
Lay abstract Ulcerative colitis (UC) is a long-term inflammatory disease affecting the gut. Understanding how UC affects the cells of the gut can help us better understand the disease. This study identified several types of RNA molecules, including circRNA, microRNAs and messenger RNAs, that were unbalanced in the colon tissue of patients with UC compared with healthy controls. A type of circRNA, called hsa_circ_0001021, regulates genes involved in healthy intestinal function. This circRNA was significantly downregulated in patients with UC and may be a potential target for future treatments.