ONECUT2 regulates proliferation and apoptosis in glioblastoma cell lines

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor associated with a high mortality rate, with an average survival time of less than two years. GBM treatment faces significant challenges due to its infiltrative nature, genetic diversity, protection by the blood-brain barrier (BBB), drug resistance, and post-treatment side effects. Transcription factors (TFs) play a crucial role in regulating gene expression during cancer initiation and progression. This study aimed to investigate the impact of altering the function of ONECUT-2 (OC-2) in GBM cells, focusing on metabolic activity, proliferation, cell cycle, and apoptosis. To confirm the successful reduction of OC-2 expression in U251 and U87 cells compared to the control cells (wild types; WT), quantitative real-time polymerase chain reaction (qPCR) was performed. The downregulation of OC-2 resulted in a significant decrease in metabolic activity (MTT) of U251 cells by 47 % (P = 0.0056) and U87 cells by 36.4 % (P = 0.0003) compared to WT cells. In U251 cells, OC-2 downregulation caused cell cycle arrest in both the G0/G1 phase (13.6 %) and the S/G2 phase (52.52 %) compared to WT cells. Similarly, in U87 cells, downregulation of OC-2 led to cell cycle arrest in the G0/G1 phase (90.5 %) and the G2 phase (76.61 %) compared to WT cells. Furthermore, OC-2 downregulation significantly affected early-stage apoptosis in U251 cells (95.46 %, P = 0.0005) and U87 cells (19.64 %, P = 0.0004). Conversely, upregulation of OC-2 significantly increased the metabolic activity (MTT) of U251 cells by 94 % (P = 0.0067) and U87 cells by 58 % (P = 0.0028) compared to WT cells. These findings highlight the essential role of OC-2 in regulating the progression of GBM cells. Consequently, OC-2 represents a potential therapeutic target for inhibiting GBM. Overall, this study demonstrates that OC-2 plays a significant role in cell progression, suggesting its potential as a therapeutic target for GBM treatment.