TFAP2A inhibits microRNA-126 expression at a transcriptional level to aggravate ischemic neuronal injury.

This study was performed to investigate the effect of transcription factor AP-2 alpha (TFAP2A) and the underlying mechanism in oxygen-glucose deprivation (OGD) cell model and transient global cerebral ischemia (tGCI) rat model. Based on CCK-8 and Hoechst staining results, silencing of TFAP2A could enhance the viability of OGD-treated PC12 cells and decrease the apoptotic rate of cells. ChIP assay was performed to detect the binding of TFAP2A to the promoter region of microRNA (miR)-126, and we found that TFAP2A could inhibit miR-126 expression. Further mechanistic investigation showed that miR-126 targeted polo like kinase 2 (PLK2), while overexpression of PLK2 activated the IκBα/NF-κB pathway and further suppressed the growth of OGD-treated PC12 cells. As for in vivo assay, proportion of infarction area in brain tissues of rats was analyzed by TTC staining, whereas Nissl staining was applied to evaluate the number of surviving brain neurons. The pathological condition of neuronal injury in rat brain tissues was monitored using HE staining. Results suggested that TFAP2A downregulated miR-126 to upregulate PLK2 and activate IκBα/NF-κB pathway, which deteriorated neuronal injury following ischemia in vivo. PMID: 33264079 [PubMed - as supplied by publisher]
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research