Circ_Slc7a11 Aggravates Intestinal Mucosa Barrier Damage by Regulating SIRT1 Acetylation Through miR-624-5p

SIRT1 plays a crucial role in the production of reactive oxygen species (ROS) and ischemia/reperfusion (I/R), yet the upstream mechanisms that directly regulate SIRT1 expression during intestinal I/R remain unclear. Recent studies have shown that noncoding RNAs, such as circular RNAs (circRNAs), are important players in physiological and pathological processes based on their multiple regulatory roles in gene expression. This study aimed to elucidate the role of SIRT1 in intestinal mucosa barrier damage and to investigate the regulation of SIRT1 by circRNA sponges. Third-degree burn mouse model was used. Before third-degree burn, mice were injected with miR-624-5pagomir or Circ_Slc7a11 siRNA intravenously. In addition, hypoxia reoxidation (H/R) was performed in vitro on Caco-2 cells to mimic an in vivo model of intestinal mucosa barrier damage. In vitro, SIRT1 deficiency significantly reduced H/R-induced ROS overproduction and acetylation levels by decreasing mitochondrial superoxide anion (O^2-) levels, inhibiting NADPH oxidase activity, and enhancing antioxidant enzyme expression. miR-624-5p was pinpointed as a direct regulator of SIRT1 expression. The circRNA transcribed from the Slc7a11 gene, called Circ_Slc7a11, regulated SIRT1 expression as a sponge of miR-624-5p. Circ_Slc7a11 silencing or miR-624-5p overexpression downregulated SIRT1 expression, and reduced oxidative stress and acetylation levels to alleviate intestinal mucosa barrier damage. Elevated Circ_Slc7a11 and decreased miR-624-5p levels were observed in mice with intestinal I/R. Our results reveal the key role of Circ_Slc7a11/miR-624-5p/SIRT1 signaling pathway in regulating oxidative stress and acetylation in intestinal mucosa barrier damage.