Morphine postconditioning-induced upregulation of lncRNA TINCR protects cardiomyocytes from ischemia-reperfusion injury via inhibiting degradation and ubiquitination of FGF1.

Our previous study has demonstrated that morphine postconditioning (MpostC) protects cardiomyocytes from ischemia/reperfusion (I/R) injury partly through activating protein kinase-epsilon (PKCepsilon) signaling pathway and subsequently inhibiting mitochondrial permeability transition pore (mPTP) opening. In this study, we aim to investigate the relationship between long non-coding RNA TINCR and PKCepsilon in cardiomyocytes under MpostC-treated I/R injury. The myocardial I/R rat model was established by the ligation of lower anterior descending coronary artery for 45 minutes followed by the reperfusion for 1 hour, and MpostC was performed before the reperfusion. The results indicated that MpostC restored the expression of TINCR in I/R rat myocardial tissues. In cardiomyocytes, the therapeutic effect of MpostC, including reduced mPTP opening, reduced Cytochrome-c expression, increased cell viability, and reduced cell apoptosis, was dramatically negated by interfering TINCR. The expression of FGF1, a protein that activates PKCepsilon signaling pathway, was positively correlated with TINCR. The RIP and RNA pull-down assay further confirmed the binding between FGF1 and TINCR. Furthermore, TINCR was demonstrated to inhibit the degradation and ubiquitination of FGF1 in cardiomyocytes using the cycloheximide experiment and the ubiquitination assay. The TINCR/FGF1/PKCepsilon axis was revealed to mediate the protective effect of MpostC against H/R injury both in vitro and in vivo. In conclusion, our findings demonstrated that MpostC-induced upregulation of TINCR protects cardiomyocytes from I/R injury via inhibiting degradation and ubiquitination of FGF1, and subsequently activating PKCepsilon signaling pathway, which provides a novel insight in the mechanism of TINCR and PKCepsilon during MpostC treatment of I/R injury.