Snail and ZEB2 play an oncogenic role in pediatric and adult glioblastoma cells through the induction of epithelial mesenchymal transition like process

Abstract

Background: The factors affecting adult and pediatric glioblastoma progression are of great clinical importance since dismal outcomes have been observed for glioblastoma patients. Here, we focused on Epithelial mesenchymal transition (EMT) related factors as a key molecular factor in determining clinical outcome. The Snail and ZEB2 genes are known to coordinate the regulation of tumor progression in diverse tumors through induction of EMT

however, its role in pediatric and adult glioblastoma is still uncertain. Therefore, we aimed to further define its role in vitro. Methods and Results: The small interfering RNA (siRNA) technique was employed to knock down Snail and ZEB2 expression in pediatric glioblastoma (KNS42) and adult glioblastoma cell lines (U87, and U373). Specific inhibition of both Snail and ZEB2 expression increased E-cadherin expression but decreased vimentin expression in all cell lines. In addition, inhibition of the expression of Snail significantly reduced the proliferation, viability, invasion, and migration of adult and pediatric glioblastoma cells as well as increased the number of cells in the G1 phase (G1 phase arrest). Also, inhibition of ZEB2 significantly reduced invasion and migration of both pediatric and adult glioblastoma cells. Interestingly, in pediatric glioblastoma, but not in adult glioblastoma cells, silencing of ZEB2 reduced cell proliferation, cell viability, and changed cell cycle progression of tumor cells, but these findings were not evoked in adult glioblastoma cells. Immunehistochemical staining for Snail and ZEB2 showed no difference between pediatric glioblastoma and adult glioblastoma. However, comparing to the immunoreactions of normal astrocytes and low grade glial tumors, glioblastoma cells showed relatively strong Snail and ZEB2 expression pattern. Also, mRNA for ZEB2 was higher in adult and pediatric glioblastoma cells than normal tissues. Conclusions: Knockdown of Snail suppressed the proliferation, viability, migration, and invasion of adult and pediatric glioblastoma cells as well as inhibited cell cycle progression by promoting EMT like process. Also, inhibition of ZEB2 significantly reduced invasion and migration of both pediatric and adult glioblastoma cells. However, in pediatric glioblastoma cells, but not in adult glioblastoma cells, silencing of ZEB2 reduced cell proliferation, cell viability, and cell cycle progression of tumor cells. Our study demonstrated that Snail and ZEB2 play an oncogenic role in pediatric and adult glioblastoma by promoting EMT like process. However, unlike Snail, ZEB2 was shown to act differently on the cell proliferation, cell viability and cell cycle progression of pediatric and adult glioblastoma cells, which suggests that pediatric and adult glioblastoma may be different in certain biology and oncogenic process.