TFAP2A inhibits microRNA-126 expression at the transcriptional level and aggravates ischemic neuronal injury.

Neuronal injury induced by cerebral ischemia poses a serious health risk globally, and there is no effective clinical therapy. This study was performed to investigate the role of transcription factor AP-2 alpha (TFAP2A) in cerebral ischemia, and the underlying mechanisms, using an in-vitro model (PC-12 cells) of oxygen-glucose deprivation (OGD), and an in-vivo model (rat) of transient global cerebral ischemia (tGCI). The results for CCK-8 and Hoechst staining showed that silencing of TFAP2A enhanced the viability and decreased the rate of apoptosis of PC12 cells subjected to OGD. ChIP assays were performed to evaluate the binding of TFAP2A to the promoter region of microRNA (miR)-126, and we found that TFAP2A inhibits the expression of miR-126. Further mechanistic investigation revealed that miR-126 targets polo like kinase 2 (PLK2), and that overexpression of PLK2 activates the IκBα-NF-κB signaling pathway and suppresses the growth of PC12 cells subjected to OGD. For our in-vivo assay, we used TTC staining to analyze the infarction area in the brain tissues of rats, and Nissl staining to evaluate the number of surviving brain neurons. The pathological conditions associated with neuronal injury in rat brain tissues were assessed by staining the tissues with hematoxylin-eosin. Our results indicate that TFAP2A downregulates miR-126, and thereby upregulates PLK2 and activates the IκBα-NF-κB pathway, which increased neuronal injury following cerebral ischemia.