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• W2793519198 abstract "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." @default.
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• W2793519198 date "2018-04-01" @default.
• W2793519198 modified "2023-10-16" @default.
• W2793519198 title "<scp>FBW</scp> 7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells" @default.
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• W2793519198 doi "https://doi.org/10.1111/cas.13528" @default.
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