Knockdown of Long Noncoding RNA IPCRL1 Mitigates Myocardial Ischemia/Reperfusion Injury via miR-185-3p/JIP3 Axis and JNK Pathway

Purpose: Myocardial ischemia/reperfusion injury (MIRI) represents a significant culprit leading to adverse consequences after cardiac surgery. This study aims to clarify the function and related pathway of ischemic preconditioning related lncRNA-1 (IPCRL1) in MIRI. Methods: MIRI model was established in C57BL/6J mice via the myocardial reperfusion method, and hypoxia/reoxygenation (H/R) model was constructed using HL-1 cell. IPCRL1, miR-185-3p, JIP3, TNF-α were determined using RT-qPCR. JIP3, c-Jun, JNK phosphorylation, B-cell lymphoma 2(BCL2), Bcl-2-associated X protein (BAX), cleaved caspase-3 levels were measured using Western blot. ELISA was used to measured cardiomyocyte injury markers and TNF-α concentrations. IHC and flow cytometry investigated the trends in apoptosis. The binding relationships between IPCRL1, miR-185-3p, JIP3 were verified by Dual-luciferase reporter assay. Results: IPCRL1 knockdown reduced infarct size, inflammation, and apoptosis. Additionally, knockdown of IPCRL1 downregulates the expression of JIP3 via sponge miRNA-185-3p, thereby affecting the JNK pathway, meanwhile inhibition of miRNA-185-3p reversed above effects. Knocking down IPCRL1 can counteract cardiomyocyte apoptosis through miR-185-3p/JIP3 axis, offering protection against MIRI. Conclusion: IPCRL1/miRNA-185-3p/JIP3 axis mediates MIRI through JNK pathway and IPCRL1 may hold promise as a new noteworthy target for MIRI.