MiR-370 accelerated cerebral ischemia reperfusion injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway

Abstract

Cerebral ischemia reperfusion (CIR) is one of the highly lethal diseases in the world. MicroRNA-370 (miR-370) exerts multiple functions in different diseases. However, further research is needed to investigate the potential role of miR-370 in CIR injury. The in vivo middle cerebral artery occlusion (MCAO) rat model and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) SH-SY5Y cell model were successfully established to mimic CIR injury. The infarct sizes of brain tissues from rats were evaluated. The relationship between miR-370 and silencing information regulatory protein 6 (SIRT6) was confirmed by luciferase activity assay. The cell viability and apoptosis were determined by CCK-8 assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining. In this study, miR-370 was upregulated in brain tissues of MCAO rats and knockdown of miR-370 decreased cerebral infarction volume of MCAO rats and it alleviated CIR injury in vivo. The in vitro experiments indicated that knockdown of miR-370 promoted cell viability and alleviated OGD/R-induced SH-SY5Y cell apoptosis. Additionally, the TargetScan predicted that SIRT6 was a target of miR-370 and confirmed by luciferase activity assay. Moreover, miR-370 inhibited SIRT6 expression and regulated Nrf2/ARE signal pathway, whereas overexpression of SIRT6 partly reversed the effect of miR-370 on OGD/R-induced SH-SY5Y cell injury. Thus, we could conclude that miR-370 accelerated CIR injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway, which might provide novel therapeutic targets for CIR injury treatment.

Keywords: MiR-370; Nrf2/ARE signal pathway; SIRT6; cerebral ischemia reperfusion injury.