Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis.

Abstract

Ulcerative colitis (UC) is characterized by chronic inflammation in the colon and epigenetic factors underlying the occurrence. Circular RNAs (circRNAs) have been under intensive focus due to the circular construct and gene-regulating functions. However, the changes and roles of circRNAs in UC remain unknown. Microarrays were used to detect the differentially expressed genes, and quantitative real-time PCR was used to identify the changes in UC. In silico analyses were performed to predict the functions of circRNAs and mRNAs. In vitro, epithelial cell lines were stimulated by pro-inflammation effectors to test the alterations in circRNAs. CircRNAs-microRNAs-mRNAs network clarified the potential mechanisms underlying circRNAs in UC. The binding site between hsa_circ_0007919 and miR-138 or let-7a was verified using dual-luciferase assay. A total of 264 significantly dysregulated circRNAs and 1869 differentially expressed mRNAs in inflamed mucosa were compared with the non-inflamed mucosa in UC. Hsa_circ_0004662 and hsa_circ_0007919 were altered largely in UC tissues. Hsa_circ_0007919 was reduced persistently after inflammatory treatments, and it was relevant to Mayo endoscopic subscores and the expression of tight junction molecules. Finally, hsa_circ_0007919 could harbor miR-138, and let-7a to regulate the targeted mRNAs EPC1 and VIPR1. Several circRNAs were differentially expressed in UC. Hsa_circ_0007919 is related to clinical characteristics and epithelial integrity by binding to hsa-let-7a, hsa-miR-138 to regulate the target genes. CircRNAs, especially hsa_circ_0007919, are associated with the pathogenesis and development of UC, with potential diagnostic and therapeutic implications.