CircPhc3 promotes the repair of intestinal mucosa after burn injury through the TRIM28-mediated hnRNPK SUMOylation stability modification mechanism.

This paper investigates the mechanism of action of circPhc3 in the repair of intestinal mucosa in mice with severe burn injuries. The expression of circPhc3 is decreased in the intestinal mucosal tissue of these mice, and its overexpression may aid in the reconstruction of the damaged mucosa. The effects of circPhc3 on cell proliferation and migration were studied in MC38 cells, with an initial assessment of its repair function in mouse intestinal mucosa. Next, trap and mass spectrometry were used to identify heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a potential target. RNA immunoprecipitation experiments confirmed the binding of circPhc3 to hnRNPK.The study highlights that the intracellular level of circPhc3 plays a crucial role in regulating the degradation and stability of hnRNPK expression. It also demonstrates that the E3 SUMO ligase, trimeric domain-containing protein 28 (TRIM28), acts as a promoter of hnRNPK stability. CircPhc3 facilitates TRIM28's binding to hnRNPK, thereby promoting hnRNPK SUMOylation. This modification inhibits ubiquitination and subsequent protein degradation.These findings reveal that SUMOylation modulates cellular hnRNPK levels and plays a key role in the mechanism of intestinal mucosal injury and repair following severe burn injuries. Furthermore, the interaction between hnRNPK SUMOylation and ubiquitination is essential for understanding intestinal mucosal repair. This study is the first to report the role of circPhc3 in promoting intestinal mucosal repair.