Fig. 8. Schematic showing the proposed mechanism for the effects of lncCIRBIL on cardiac ischemia–reperfusion injury.

LncCIRBIL localizes in the cytoplasm of cardiomyocytes where it binds Bclaf1 protein to prevent its translocation to the nucleus. During cardiac ischemia–reperfusion injury, lncCIRBIL expression is reduced, which favors the dissociation of Bclaf1 protein from its binding state to become free for nuclear translocation. After entering the nucleus, Bclaf1 activates the transcription of p53 and Bax to induce cardiomyocyte apoptosis leading to cardiac ischemia–reperfusion injury. Meanwhile, p53 negatively regulates the transcription of lncCIRBIL and upregulation of p53 causes further downregulation of lncCIRBIL. Based on these findings, a novel positive feedback regulatory circuit is proposed: I/R or H/R → lncCIRBIL↓ → Bclaf1↑ → p53↑ → lncCIRBIL↓ → I/R or H/R injury↑.