MicroRNA-152-3p protects neurons from oxygen-glucose-deprivation/reoxygenation-induced injury through upregulation of Nrf2/ARE antioxidant signaling by targeting PSD-93

• Published in: Biochemical and biophysical research communications Vol. 517; no. 1; pp. 69 - 76
• Main Authors: Zhang, Aixiang, Qian, Yuanjie, Qian, Jian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.09.2019
• Subjects: Animals; Antioxidant Response Elements; Apoptosis; Cell Line; Glucose - metabolism; Guanylate Kinases - genetics; Guanylate Kinases - metabolism; Ischemic stroke; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miR-152-3p; Neurons - cytology; Neurons - metabolism; Neurons - pathology; Neuroprotection; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxygen - metabolism; Oxygen-glucose deprivation/reoxygenation; PSD-93; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Signal Transduction; Up-Regulation; PSD-93; Ischemic stroke; Oxygen-glucose deprivation/reoxygenation; miR-152-3p; Nrf2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.07.012

MicroRNAs (miRNAs) have emerged as critical regulators of ischemic stroke, a condition that affects neuronal survival. However, the precise role of miRNAs in regulating neuronal injury during ischemic stroke remains largely unknown. In this study, we investigated the potential role of miR-152-3p in regulating oxygen-glucose-deprivation/reoxygenation (OGD/R)-induced neuronal injury in vitro. We found that OGD/R-exposed neurons expressed less miR-152-3p. Functional analysis revealed that miR-152-3p overexpression increased the viability and reduced the apoptosis and reactive oxygen species (ROS) production of OGD/R-exposed neurons. By contrast, miR-152-3p inhibition exacerbated OGD/R-induced injury. Notably, we identified postsynaptic density protein-93 (PSD-93), an important regulator of neuroprotection during ischemic stroke, as a miR-152-3p target gene. PSD-93 inhibition by small interfering RNA (siRNA) or miR-152-3p reinforced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) antioxidant signaling in OGD/R-exposed neurons. However, PSD-93 overexpression or Nrf2 silencing partially reversed miR-152-3p-mediated neuroprotection in OGD/R-exposed neurons. Overall, these results demonstrated that miR-152-3p protected neurons from OGD/R-induced apoptosis and ROS production by reinforcing Nrf2/ARE antioxidant signaling through targeting and inhibiting PSD-93, findings that suggest miR-152-3p is a potential target for neuroprotection during ischemic stroke. [Display omitted] •miR-152-3p is decreased in neurons exposed to OGD/R.•miR-152-3p overexpression alleviates OGD/R-induced neuronal injury.•.PSD-93 is identified as a target gene of miR-152-3p.•PSD-93 regulates OGD/R-induced neuronal injury by Nrf2 signaling.•miR-152-3p/PSD-93/Nrf2 signaling regulates OGD/R-induced neuronal injury.