Circular RNAs in inflammatory bowel disease: A review of mechanisms, biomarkers and therapeutic potential

Li Jun Yang ^1* Min Tang ¹ Le Yang ² Ling Nan He ³ Hua Hui Li ⁴

• ¹ Department of Pharmacy, Yiyang Medical College, Yiyang, China
• ² Department of Gastroenterology, Yiyang Central Hospital, Yiyang, China
• ³ Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
• ⁴ Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China

Inflammatory bowel disease (IBD) is an autoimmune disease of unknown etiology characterized by recurrent chronic inflammation of the gastrointestinal tract. The incidence of IBD is increasing and has become a focus of research on digestive diseases. Despite advances in understanding its multifactorial etiology, including genetic predisposition, microbiome dysbiosis, and immune dysregulation. However, the molecular mechanisms driving IBD pathogenesis remain incompletely elucidated.Circular RNA (circRNA) is a stable single-stranded RNA with a closed-loop structure and conserved nature. circRNA possesses multiple functions, such as adsorption of microRNAs and RNA-binding proteins, and is involved in the regulation of gene splicing and transcription, as well as protein translation. However, circRNAs in IBD progression and their clinical potential as biomarkers or therapeutic targets are yet to be systematically explored. In this review, we comprehensively synthesize recent advancements in circRNA research related to IBD, integrating evidence from in vitro, in vivo, and clinical studies. We systematically analyze aberrant circRNA expression profiles in IBD tissues (e.g., intestinal mucosa, peripheral blood, and exosomes) and discuss their mechanism of action contributions to inflammation, intestinal epithelial barrier dysfunction, autophagy, intestinal fibrosis, and colitis-associated cancer (CAC). Furthermore, we evaluate methodologies for circRNA detection and therapeutic modulation, including RNA interference, viral vector delivery, and PLGA MSs delivery system strategies. This review highlights the potential of circRNA-focused strategies in the diagnosis and treatment of IBD, offering a scientific foundation for advancing precision medicine in IBD management.