Long non-coding NEAT1 weakens the protective role of sevoflurane on myocardial ischemia/reperfusion injury by mediating the microRNA-140/RhoA axis

Abstract

The function of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been revealed in injury caused by myocardial ischemia/reperfusion (I/R), however, its association with Sevoflurane (Sev), an anesthetic effective for regulating inflammation and oxidative stress, is not yet clear in I/R injury. The aim of this study was to functionally validate and elucidate the mechanism-of-action for Sev-mediated NEAT1 in myocardial I/R injury. Firstly, reduced NEAT1 was revealed in myocardial I/R injured mice treated with Sev. Moreover, restoration of NEAT1 could repress the alleviating role of Sev in cardiac function, infarct size and myocardial apoptosis in mice, while miR-140 was remarkably enhanced in myocardial tissues from mice treated with Sev. Furthermore, miR-140 was suggested and authenticated as a downstream biomolecule of NEAT1 with the help of a bioinformatics tool. Interestingly, miR-140 inhibitor played the same role as NEAT1 overexpression on the cardiac function, infarct size and apoptosis of mice. Finally, it was manifested that RhoA was a putative target of miR-140, which functioned importantly in the Sev/miR-140-mediated myocardial I/R injury. All in all, NEAT1 knockdown contributed to Sev-mediated myocardial I/R injury alleviation via the miR-140/RhoA axis.