Fig. 8: Schematic illustration of the mechanism whereby circEZH2_005 regulates Gprc5a stabilizing via hnRNPA1.

In general, circEZH2_005 is mainly expressed in intestinal crypt cells. After I/R injury, the expression of circEZH2_005 is decreased in the Lgr5+ stem cells and plasma exosomes. Meanwhile, the reduced expression of circEZH2_005 results in decreased hnRNPA1 binding and cytoplasmic export, thus inhibiting the binding of hnRNPA1 to Gprc5a. Therefore, Gprc5a becomes free and is degraded in the cytoplasm, which may alter the expression of Gprc5a-regulated proliferation genes. Consequently, reduced circEZH2_005 expression aggravates the I/ R-induced Lgr5+ stem cell injury, contributing to the development and progression of intestinal I/R injury.