Overexpression of Epsin�3 enhances migration and invasion of glioma cells by inducing epithelial‑mesenchymal transition

Epsin 3 (EPN3) expression is limited to gastric parietal cells and wounded or pathological tissue rather than normal brain tissue, and although it has been identified as an oncogene in estrogen receptor‑positive breast cancer and non‑small cell lung cancer, its function in cancer is poorly understood. The present study aimed to investigate the association of EPN3 expression with the clinicopathological features of patients with glioma, as well as the effects of EPN3 on glioblastoma cells and the potential molecular mechanisms for its effects on glioblastoma cell behavior. EPN3 expression was assessed by immunohistochemistry in tissue samples from 167 patients with glioma, as well as by western blotting in 5 glioblastoma cell lines. The U87 and U251 glioblastoma cell lines were used to investigate the effects of EPN3 on glioblastoma cell invasion and migration through gain and loss of EPN3 expression experiments; expression levels were further investigated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses. The results demonstrated that EPN3 expression levels were upregulated in high‑grade glioma tissues compared with low‑grade tissues, and there were varying expression levels of EPN3 in the five glioblastoma cell lines. No significant differences were observed in EPN3 expression in relation to patient age, sex or tumor size. Overexpression of EPN3 promoted glioblastoma cell migration and invasion, which we hypothesized was through affecting epithelial‑mesenchymal transition (EMT). RT‑qPCR and western blotting revealed that EPN3 upregulation increased the expression of Notch1 intracellular domain, β‑catenin, Slug, Twist and zinc‑finger E‑box‑binding homeobox (ZEB)‑1. These results suggested that EPN3 enhances the migration and invasion of glioblastoma cells by activating the transcription factors Slug, Twist and ZEB1, but not Snail 1 or ZEB2, to induce EMT in glioma cells; EPN3 involvement in the Notch and WNT/β‑catenin signaling pathways may contribute to this process.