Suppression of microRNA-144-3p attenuates oxygen-glucose deprivation/reoxygenation-induced neuronal injury by promoting Brg1/Nrf2/ARE signaling

Abstract

Accumulating evidence has reported that microRNA-144-3p (miR-144-3p) is highly related to oxidative stress and apoptosis. However, little is known regarding its role in cerebral ischemia/reperfusion-induced neuronal injury. Herein, our results showed that miR-144-3p expression was significantly downregulated in neurons following oxygen-glucose deprivation and reoxygenation (OGD/R) treatment. Overexpression of miR-144-3p markedly reduced cell viability, promoted cell apoptosis, and increased oxidative stress in neurons with OGD/R treatment, whereas downregulation of miR-144-3p protected neurons against OGD/R-induced injury. Brahma-related gene 1 (Brg1) was identified as a potential target gene of miR-144-3p. Moreover, downregulation of miR-144-3p promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased antioxidant response element (ARE) activity. However, knockdown of Brg1 significantly abrogated the neuroprotective effects of miR-144-3p downregulation. Overall, our results suggest that miR-144-3p contributes to OGD/R-induced neuronal injury in vitro through negatively regulating Brg1/Nrf2/ARE signaling.

Keywords: Brg1; Nrf2; OGD/R; cerebral ischemia/reperfusion injury; miR-144-3p.