Relationship Between Activating Transcription Factor 3 and Forkhead Box Protein A2 in Spinal Cord Injury and the Underlying Mechanism.

Activating transcription factor 3 (ATF3) may function as a regulator of various diseases; however, its role in spinal cord injury (SCI) remains unknown. We designed a current work to evaluate the potentials of the ATF3/forkhead box protein A2 (FOXA2) axis in SCI. GSE45006 chip was analyzed, and a volcano plot and heatmap were drawn. Gene Ontology and KEGG analysis were performed for the differentially expressed genes. Animals with SCI were established. Quantitative reverse transcription polymerase chain reaction and western blotting were used to determine mRNA expression, and western blotting was used for detecting protein expression. The interaction between FOXA2 and the ATF3 promoter was evaluated using the UCSC database and confirmed using dual-luciferase and chromatin immunoprecipitation assays. Cellular behaviors were determined using CCK-8, EdU, and TUNEL assays. Levels of p-PI3K, PI3K, p-AKT, and AKT were examined by the WB method. We found that ATF3 expression was markedly increased in rats with SCI. Interestingly, ATF3 knockdown increased the proliferation and suppressed the apoptotic ability of PC12 cells. FOXA2 activates ATF3 transcription. Knockdown of FOXA2-mediated down-regulation of ATF3 increases growth and decreases PC12 cell death. ATF3 knockdown could increase the level of p-PI3K and p-AKT; FOXA2 shRNA could affect the expression of p-PI3K and p-AKT, which was partially abrogated by ATF3 OE. Forkhead box protein regulates the transcription of ATF3, thereby affecting cell growth and PC12 cell death.