CircSOD2: Disruption of intestinal mucosal barrier function in ulcerative colitis by regulating the miR-378g/Snail1 axis.

Abstract

Circular RNA (circRNA) has been found to mediate ulcerative colitis (UC) progression by regulating intestinal mucosal barrier function. However, the role of circSOD2 in UC process and its underlying molecular mechanism still need to be further elucidated. Lipopolysaccharide (LPS)-induced Caco2 cells were used to mimic UC cell models. CircSOD2, miR-378g, and Snail1 levels were determined by quantitative real-time PCR. Cell viability was detected using MTT assay, and inflammatory cytokine levels were measured using ELISA. The intestinal mucosal barrier function was evaluated by testing transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran permeability. Snail1 and tight junction-related markers (Zo-1 and Claudin2) protein levels were examined using western blot. The interaction between miR-378g and circSOD2 or Snail1 was confirmed by dual-luciferase reporter assay. Dextran sulfate sodium (DSS) was used to induce UC rat models in vivo. CircSOD2 was overexpressed in UC patients, and its knockdown significantly increased cell viability, transepithelial electrical resistance, and tight junction-related protein expression, while reduced inflammation cytokine levels and the permeability of FITC-dextran in LPS-induced Caco2 cells. In terms of mechanism, circSOD2 sponged miR-378g to positively regulate Snail1 expression. MiR-378g inhibitor reversed the effect of circSOD2 knockdown on intestinal mucosal barrier injury and Snail1 expression in LPS-induced Caco2 cells. In DSS-induced UC rat models, circSOD2 knockdown also could repair the intestinal mucosal barrier injury through regulating miR-378g/Snail1 axis. CircSOD2 could destroy intestinal mucosal barrier function in LPS-induced Caco2 cells and DSS-induced UC rats by miR-378g/Snail1 axis.