Inhibition of miR-143 during ischemia cerebral injury protects neurones through recovery of the hexokinase 2-mediated glucose uptake

Ischemic stroke, a major cause of death, is caused by occlusion of a blood vessel, resulting in significant reduction in regional cerebral blood flow. MiRNAs are a family of short noncoding RNAs (18-22 nts) and bind the 3'-UTR of their target genes to suppress the gene expression post-transcriptionally. In the present study, we report that miR-143 is down-regulated in rat neurones but highly expressed in astrocytes. In vivo middle cerebral artery occlusion (MCAO) and ex vivo oxygen-glucose deprivation (OGD) results showed that miR-143 was significantly induced by ischemia injury. Meanwhile, we observed suppression of glucose uptake and lactate product of rat brain and primary neurones after MCAO or OGD. The glycolysis enzymes hexokinase 2 (HK2), PKM2, and LDHA were inhibited by MCAO or OGD at protein and mRNA levels. In addition, overexpression of miR-143 significantly inhibited HK2 expression, glucose uptake, and lactate product. We report that HK2 is a direct target of miR-143. Importantly, restoration of HK2 in miR-143 overexpressing rat neurones recovered glucose uptake and lactate product. Our results demonstrated inhibition of miR-143 during OGD could protect rat neuronal cells from ischemic brain injury (IBI). In summary, the present study reveals a miRNA-mediated neuron protection during IBI, providing a new strategy for the development of therapeutic agents against IBI.