Journal of King Saud University: Science (Feb 2024)
ONECUT2 regulates proliferation and apoptosis in glioblastoma cell lines
Abstract
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.
