Protein disulfide isomerase A4 (PDIA4) is highly expressed in clear cell ovarian
carcinoma and
lung cancer. Through analysis of TCGA database and CGGA database, we noted that PDIA4 is a key promotor of
glioblastoma (GBM). However, the detailed role and molecular mechanism of PDIA4 in GBM remain unclear. In this study, the expression pattern and biological role of PDIA4 in GBM was investigated. PDIA4 was overexpressed in GBM
tumor samples and cell lines and positively correlated with pathological grades in
glioma patients. In addition, downregulation of PDIA4 promoted apoptosis and inhibited proliferation of GBM. Meanwhile, there was a concurrent decrease in aerobic glycolysis metabolites. Mechanistically, PDIA4 downregulation promoted the apoptosis of GBM cells by increased the expression of apoptosis pathway
proteins (
caspase 3,
caspase 9 and Bax). Downregulation of PDIA4 decreased energy demand and inhibited GBM growth in vitro and in vivo. Besides, such effect also inhibited the PI3K/AKT/m-TOR pathway by inhibiting
protein phosphorylation levels of PI3K, AKT and m-TOR. After addition of PI3K/AKT/mTOR pathway activator
740Y-P, the effect of PDIA4 knockdown on GBM was reversed. Therefore, we believe that PDIA4 regulates the proliferation via activating the PI3K/AKT/m-TOR pathway and suppression of apoptosis in
glioblastoma. It could be used as a potential target for the treatment of GBM.