The circular RNA Phc3 promotes the repair of damage to the intestinal mucosal barrier by regulating the miR-93/PHF6 and ACTN4 pathways.

BACKGROUND

Non-coding RNAs, such as circular RNAs (circRNAs), are abundant in the human body and can influence the development and progression of various diseases. However, the role they play in repairing intestinal mucosal damage remains unclear.

METHOD: RT-qPCR was used to analyse the expression levels of circRNA and messenger RNA in burn-damaged intestinal mucosa. The localisation of circPhc3 was examined using fluorescence in situ hybridisation (FISH) technology. The effects of circPhc3 overexpression were validated at the functional level in CCK8 and scratch assay models through in vitro and in vivo experiments. At the mechanistic level, techniques including immunohistochemical staining, chromatin immunoprecipitation (ChIP), luciferase reporter assays, Western blotting, tandem affinity purification with mass spectrometry (TRAP-MS) analysis and RNA immunoprecipitation (RIP) were employed.

RESULTS

Circular Phc3 (circPhc3) was found to be downregulated in the intestinal mucosa of burn-injured mice. High expression of this protein was found to correlate positively with the integrity of damaged intestinal mucosa. In vitro and in vivo experiments revealed that the overexpression of circPhc3 significantly enhances the migration and proliferation capacity of mouse intestinal epithelial cells. Analysis of the molecular mechanism indicates that circPhc3 binds specifically to miR-93, thereby upregulating PHF6 expression and ultimately promoting cellular proliferation and migration. Additionally, circPhc3 recruits the ACTN4 protein, thereby facilitating the repair process of the intestinal mucosa.

CONCLUSION

Taken together, these findings reveal that circPhc3 promotes both cell migration and proliferative capacity through two mechanisms: the ceRNA sponge mechanism and RNA-binding proteins (RBPs). This accelerates the repair of damaged intestinal mucosa.