Inhibition of Bmi1 suppresses tumorigenicity in glioma stem cells via the YAP/Pax3 pathway

Glioma stem cells (GSCs) are related to the recurrence of glioblastoma multiforme (GBM) due to their resistance to chemotherapy (CT) and radiotherapy (RT). Bmi1 is associated with self-renewal of malignant cancer stem cells (CSCs). The aim of this study was to evaluate the effect of Bmi1 downregulation in GSCs to target and eradicate CSCs in malignant tissues. A series of experiments involving Bmi1 knockdown, MTS assay, Pax3 and YAP overexpression, quantitative real-time PCR (qRT-PCR), western blotting, BrdU incorporation assay, and soft agar assay were performed in this study. Knockdown of Bmi1 notably suppressed GSC proliferation as shown in BrdU-positive, Bmi1-knockdown cells. Additionally, mRNA and protein expression levels of Pax3 were suppressed in Bmi1-knockdown cells, as shown by western blot and qRT-PCR results. Excessive Pax3 expression in Bmi1-knockdown cells attenuated the suppressive effect of Bmi1 knockdown on GSC proliferation. Pax3 expression was modulated by Bmi1 via the YAP pathway. Moreover, Pax3 modulated Bmi1 activity in GSCs. The above findings indicate that Bmi1 activity is involved in the proliferation and transformation of GSCs in GBM.