Upregulation of miR-489-3p Attenuates Cerebral Ischemia/Reperfusion Injury by Targeting Histone Deacetylase 2 (HDAC2)

ischemia/reperfusion (I/R) injury is the continuation and deterioration of ischemic injury, and there are no effective treatment strategies for this condition. It has been reported that microRNAs (miRNAs) are considered as potential targets to protect the brain against I/R injury. Previous studies have shown that miR-489-3p plays a vital role in regulating apoptosis of neurons. miR-489-3p is considered as a potential target to pro-tect the brain against I/R injury-induced neuron apoptosis. This study aimed to explore the molecular mechanism of miR-489-3p in protection against cerebral I/R injury. A rat model with cerebral I/R injury was established using the MCAO method. The cell model was constructed using the oxygen glucose deprivation (OGD) method. The expression of miR-489-3p was detected by qRT-PCR. The expression of HDAC2 was detected by Western blot assay and immunofluorescence assay. Cell apoptosis was evaluated by flow cytometry and TUNEL staining assay. The relationship between miR-489-3p and HDAC2 was determined by bioinformatics analysis and lucifer-ase reporter assay. Rescue experiments were performed to investigate the mechanism of the miR-489-3p/HDAC2 axis. miR-489-39 was significantly downregulated, while HDAC2 was upregulated during cerebral I/R injury both in vitro and in vivo. Upregulation of miR-489-3p obviously attenuated cerebral I/R injury by increasing PC12 cell viability, reducing LDH release, and inhibiting cell apoptosis. HDAC2 was identified as a direct target of miR-489-3p. Silencing of HDAC2 showed a neuroprotective effect against OGD/R injury in vitro. Overexpression of HDAC2 significantly attenuated the protective effects of miR-489-3p mimics on cell injury in vitro. Our results revealed that the upregulation of miR-489-3p attenuated cerebral I/R injury by negatively regulating HDAC2. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

miR-489-3p attenuates cerebral I/R injury by negatively regulating HDAC2.