Identification of the Antioxidant Enzyme B166 as a Novel Biomarker for Patients With Glioblastoma Multiforme

This study aimed to explore the regulatory role of sterol regulatory element-binding protein 1 (SREBP1) in the antioxidant enzyme B166 and to examine the prognostic and therapeutic potential of B166 in glioblastoma multiforme (GBM). RNA-seq data from TCGA and GTEX databases were analyzed to explore the relationship between B166 and GBM, as well as between B166 and SREBP1. Functional experiments were performed to determine whether SREBPs could regulate B166 expression level and to identify the major regulator of B166. Immunofluorescence staining was performed to investigate the cellular distribution of B166 in GBM. Quantitative reverse transcription polymerase chain reaction was employed to determine the regulatory effects of SREBP1-a. CellROX Deep Red dye was applied to detect mitochondrial Reactive Oxygen Species (ROS) levels. The results revealed that B166 protein was significantly upregulated in GBM tissues compared with lower-grade gliomas and normal brain tissues (p<0.0001). The B166 expression level was elevated through SREBP1-a-mediated regulation in GBM, simultaneously decreasing endogenous ROS levels to maintain cellular redox homeostasis and preserve normal mitochondrial function. Reducing SREBP1 level decreased both RNA and protein expression levels of B166. Overexpression of the active form of SREBP1-a elevated the protein levels of B166 in both the mitochondria and nucleus. Pharmacological suppression of SREBP1 or genetic inhibition of B166 disrupted redox homeostasis, resulting in elevated oxidative stress and rapid cell death. In conclusion, B166 may serve as a promising therapeutic target for GBM. Its overexpression could enhance ROS elimination, highlighting its potential therapeutic benefits for GBM patients.

B166; glioblastoma multiforme; lipid metabolism; reactive oxygen species; sterol regulatory element-binding protein 1.