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F‐box and  WD  repeat domain‐containing 7 ( FBW 7) is a  SCF ‐type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressors, it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of  FBW 7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide ( TMZ )‐based therapy. Clinical tissues and  TCGA  database analysis revealed that  FBW 7 expression was correlated inversely with glioma histology and positively with patient survival time. Lentivirus transfection‐induced  FBW 7 overexpression significantly suppressed proliferation, invasion and migration of U251 and U373 cells, whereas knockdown of  FBW 7 by targeted sh RNA  promoted proliferation, invasion and migration of glioma cells. Most importantly, the expression level of  FBW 7 was found to affect the 50% inhibitory concentration ( IC 50) of U251 and the  TMZ ‐resistant variant. Combining  TMZ  with  FBW 7 overexpression notably increased the cytotoxicity compared to  TMZ  treatment alone, which was conversely attenuated by  FBW 7 knockdown. Moreover, flow cytometry ( FC ) analysis showed overexpression of  FBW 7,  TMZ  or the combination‐increased proportion of G2/M arrest and the apoptotic rate, whereas  FBW 7 inhibition reduced G2/M arrest and apoptosis in U251 cells. Finally, mechanistic study found that  FBW 7 overexpression downregulated Aurora B, Mcl1 and Notch1 levels in a time‐dependent pattern and this expressional suppression was independent of  TMZ . These findings collectively demonstrate the critical role of  FBW 7 as a prognostic factor and a potential target to overcome chemoresistance of glioblastoma.

FBW 7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells