Background: Glioblastoma multiform (GBM) is among the commonly diagnosed brain malignancies with poor prognosis. CD133 has been introduced as an oncogene in various cancers, like GBM. This study aimed to investigate the significance of CD133 in GBM development using in silico and in vitro techniques.
Method: The TCGA-GBM database was analyzed for the correlational and comparative studies. After selecting the U87MG cell line, CD133-siRNA was transfected into U87MG cells and treated with temozolomide. The cell viability, cell cycle, migration, clonogenicity, and apoptosis of groups were investigated using MTT, flow cytometry, wound-healing, colony formation, and annexin V/PI assays. Using qRT-PCR method, the mRNA expression levels of MMP16, SOX2, RAF1, MAP2K1, MAPK3, PIK3CA, AKT3, mTOR, CDK4, and BCL2 were studied.
Results: CD133 silencing improves apoptosis rate, arrests the cell cycle at the sub-G1 phase, suppresses the clonogenicity of U87MG cells, and inhibits the PI3K/Akt and MAPK pathways via downregulating the RAF1, MAP2K1, MAPK3, PIK3CA, AKT3, and mTOR expression. Besides, combining CD133 silencing with temozolomide treatment considerably inhibits the migration of U87MG cells compared to temozolomide monotherapy.
Conclusion: CD133 can regulate the PI3K/Akt and MAPK pathways and modulate the clonogenicity, apoptosis, and cell cycle of GBM. Combining CD133 silencing with temozolomide treatment considerably increases apoptosis, arrests the cell cycle at the sub-G1, and suppresses migration of U87MG cells compared to temozolomide monotherapy.
Keywords: CD133; Glioblastoma; MAPK; PI3K/Akt; Temozolomide.
© 2024. The Author(s).