Investigating the Impact of hsa_circ_0005255 on Proliferation and Autophagy in Crohn's Disease Intestinal Epithelial Cells Through miR-23a-3p-Mediated NCOA3 Expression.

Abstract

Crohn's Disease (CD), an inflammatory bowel disorder, is influenced by genetic, immune, and environmental factors. The present study highlights the pioneering role of circular RNAs (circRNAs) in the etiology of CD, with a specific focus on hsa_circ_0005255 and its regulatory role. Utilizing both bioinformatic and experimental approaches, we exposed the mechanistic and therapeutic significance of hsa_circ_0005255 within the pathophysiological framework of CD. Our findings revealed a significant underexpression of hsa_circ_0005255 in tissue samples from CD patients and in DSS-induced CD mouse models. The overexpression of hsa_circ_0005255 markedly mitigated inflammatory responses, as indicated by decreased serum levels of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and reduced histopathological indications of inflammation in colonic tissues. It substantially improved the integrity of the epithelial barrier, evidenced by the upregulation of Zonula Occludens-1 expression and the reduction of apoptosis in colonic epithelial cells. Furthermore, this regulatory effect extended to the enhancement of epithelial cell proliferation and autophagy, characterized by the elevated expression of Ki-67, microtubule-associated protein 1A/1B-light chain 3 II, and Beclin-1, along with the suppression of cleaved caspase-3 and sequestosome 1. Mechanistically, hsa_circ_0005255 functioned as a competitive endogenous RNA, absorbing miR-23a-3p and thereby regulating Nuclear Receptor Coactivator 3. This investigation not only broadens our understanding of the involvement of circRNAs in CD pathogenesis but also identifies hsa_circ_0005255 as a potent biomarker and therapeutic target.