LINC-ROR regulates myocardial ischemia/reperfusion injury via targeting of miR-129-5p/Hook3 axis

Abstract

Purpose: To investigate the underlying mechanism of long intergenic non-protein coding RNA (LINC- ROR) in myocardial ischemia/reperfusion (I/R) injury. Methods: Rat H9C2 cells were used to establish the model of hypoxia/reoxygenation (H/R). Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The proportion of apoptotic H9C2 cells was evaluated using flow cytometry. Luciferase reporter experiments and RNA pull-down assays were used to determine the relationships among LINC-ROR, miR-129-5p, and hook microtubule tethering protein 3 (Hook3), while QRT-PCR and western blots were used to investigate the relationship between LINC-ROR and the expression and activation of Hook3 and proteins of the PI3K/AKT/mTOR pathway. Results: LINC-ROR was elevated under H/R stimulation. The viability of H9C2 cells decreased, and cell apoptosis was induced after H/R treatment. These latter effects were abrogated by the down- regulation of LINC-ROR. Luciferase reporter results and RNA pull-down showed that LINC-ROR served as the miR-129-5p sponge, and miR-129-5p was bound to Hook3 RNA directly. Moreover, overexpression of LINC-ROR increased Hook3 protein level by serving as miR-129-5p sponge. Furthermore, the overexpression of LINC-ROR activated PI3K/Akt/mTOR pathway by regulating Hook3. Conclusion: LINC-ROR increases in cardiomyocytes with H/R injury. Down-regulation of LINC-ROR alleviates myocardial I/R injury via miR-129-5p/Hook3 axis. Therefore, LINC-ROR is a potential therapeutic target for myocardial I/R injury.