Circular RNAs in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a term encompassing a few chronic inflammatory disorders that leads to damage of the intestinal tract. Although much progress has been made in understanding the pathology of IBD, the precise pathogenesis is not completely understood. Circular RNAs (circRNAs) are single-stranded, covalently closed, endogenous molecules in eukaryotes with a variety of biological functions. CircRNAs have been shown to have regulatory effects in many diseases, such as cancer, cardiovascular disease, and neurological disorders. CircRNAs have also been found to play important roles in IBD, and although they are not sufficiently investigated in the context of IBD, a few circRNAs have been identified as potential biomarkers for the diagnosis and prognosis of IBD and as potential therapeutic targets for IBD. Herein, we survey recent progress in understanding the functions and roles of circRNAs in IBD and discuss their potential clinical applications.

Keywords: circular RNA; inflammation; inflammatory bowel disease; intestinal epithelial barrier; pathogenesis.

Figure 1

Pathogenesis of IBD. Disruption of the intestinal epithelial barrier leads to the invasion of bacteria and other antigens, which triggers a series of inflammatory reactions and ultimately leads to intestinal inflammation. Th1, type 1 T helper cells; Th2, type 2 T helper cells; Th17, type 17 T helper cells.

Figure 2

Biogenesis and functions of circRNAs. CircRNAs are predominantly the products of back-splicing events that connect an exon to a preceding exon, resulting in a covalently closed exonic circRNA (I). Retention of internal introns may lead to the production of exon–intron circRNAs (EIcircRNAs) that contain sequences of exons and introns. The intronic lariats that are not branched form circular intronic RNAs (ciRNAs). EIcircRNAs associate with RNA pol II and enhance the transcription of their parental genes via an interaction with U1 snRNP (II). CiRNAs accumulate in the nucleus to regulate gene transcription in cis by promoting Pol II activity on their parental genes (III). In the cytoplasm, circRNAs may act as miRNA sponges (IV); interact with proteins, including RNA-binding proteins (RBPs) (V); and be translated into proteins (VI). CircRNAs may also be used as biomarkers of disease (VII).