C/EBP? mediates NQO1 and GSTP1 anti-oxidative reductases expression in glioblastoma, promoting brain tumor proliferation.

ABSTRACT: Glioblastoma (GBM) is the most common and most aggressive brain tumor, associated with high levels of reactive oxidative species (ROS) due to metabolic and signaling aberrations. High ROS levels are detrimental to cells, but it remains incompletely understood how cancer cells cope with the adverse effects. Here we show that C/EBP?, a ROS responsive transcription factor, regulates the transcription of NQO1 and GSTP1, two antioxidative reductases, which neutralize ROS in the GBM and mediates their proliferation. C/EBP? is upregulated in EGFR overexpressed GBM cells, inversely correlated with the survival rates of brain tumor patients. Interestingly, C/EBP? binds the promoters of NQO1 and GSTP1 and escalates their expression. Overexpression of C/EBP? selectively decreases the ROS in EGFR-overexpressed U87MG cells and promotes cell proliferation via upregulating NQO1 and GSTP1; whereas knocking down C/EBP? elevates the ROS and reduces proliferation by repressing the reductases. Accordingly, C/EBP? mediates the brain tumor growth in vivo, coupling with NQO1 and GSTP1 expression and ROS levels. Hence, C/EBP? regulates the expression of antioxidative reductases and balances the ROS, promoting brain tumor proliferation.

SUBMITTER: Lei K 

PROVIDER: S-EPMC7287278 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature