Background
OTUB1, an essential deubiquitinating enzyme, is upregulated in various types of cancer. Previous studies have shown that OTUB1 may be an oncogene in glioblastoma multiforme (GBM), but its specific regulatory mechanism remains unclear. This study aimed to investigate the mechanism by which OTUB1 and the JAK2/STAT1 signaling pathway co-regulate the growth of GBM.
Conclusion
Our study reveals a novel mechanism by which OTUB1 inhibits the JAK2/STAT1 signaling pathway. This contributes to a better understanding of OTUB1's role in GBM and provides a potential avenue for targeted therapeutic intervention.
Methods
Using bioinformatics, GBM tissues, and cells, we evaluated the expression and clinical significance of OTUB1 in GBM. Subsequently, we explored the regulatory mechanisms of OTUB1 on malignant behaviors in GBM in vitro and in vivo. In addition, we added the JAK2 inhibitor AZD1480 to explore the regulation of OTUB1 for JAK2/STAT1 pathway in GBM.
Results
We found that OTUB1 expression was upregulated in GBM. Silencing OTUB1 promotes apoptosis and cell cycle arrest at G1 phase, inhibiting cell proliferation. Moreover, OTUB1 knockdown effectively inhibited the invasion and migration of GBM cells, and the opposite phenomenon occurred with overexpression. In vivo experiments revealed that OTUB1 knockdown inhibited tumor growth, further emphasizing its crucial role in GBM progression. Mechanistically, we found that OTUB1 was negatively correlated with the JAK2/STAT1 pathway in GBM. The addition of the JAK2 inhibitor AZD1480 significantly reversed the effects of silencing OTUB1 on GBM.