E2F transcription factor 8 promotes proliferation and radioresistance in glioblastoma.

Glioblastoma (GBM) is the most lethal brain tumor that has a median survival of less than 2 years. Tumor heterogeneity and high therapeutic resistance are hallmarks of GBM. Transcription factors (TFs) play a critical role in tumor progression by regulating the transcriptional events associated with tumor cells transition into more malignant cellular phenotypes. The E2 F transcription factor 8 (E2 F8) is a recently identified TF in the E2 F family. Studies have revealed that E2 F8 is involved in tumorigenesis of multiple cancer types; however, the oncogenic role of E2 F8 in GBM was rarely studied and the prognostic value of E2 F8 has not been explored. In this study, we investigated the expression profile, prognosis correlation and oncogenic role of E2 F8 to explore its potential use as a GBM therapeutic target. E2 F8 was significantly enriched in GBM compared with normal brain tissues and low-grade glioma. E2 F8 high expression was strongly associated with worse outcome of GBM patients. E2 F8 silencing significantly attenuated the proliferation of tumor cells in vitro and tumorigenicity in vivo, while its overexpression promoted the proliferation of GBM tumor cells. Bioinformatics analysis revealed that E2 F8 was tightly linked to multiple oncogenic processes in GBM, including aggressive cell cycle, DNA repair, STAT3, TGFRβ and WNT pathways. E2 F8 high expression correlated with the expression of a variety of well-known oncogenes in GBM. E2 F8 was identified as a crucial transcriptional regulator of CHEK1 via its directly binding CHEK1 promoter area. Finally, E2 F8 conferred significant radioresistance to GBM tumor cells in vitro and in vivo. E2 F8 is highly expressed in GBM and associated with worse outcome in GBM patients. It promotes tumorigenesis and radioresistance of GBM tumor cells and has oncogenic roles via its involvement in multiple oncogenic processes and pathways such as the regulation of CHEK1 transcriptional activity.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.