BORIS/CTCFL Reprograms Glioblastoma Transcriptional Networks through the Regulation of Tumor-Associated Genes such as CD36 and FBN2

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by extensive transcriptional and epigenetic dysregulation. Brother of the Regulator of Imprinted Sites (BORIS/CTCFL) has been implicated in oncogenic transcriptional programs in several cancers, but its role in GBM remains poorly defined. This study aimed to characterize BORIS-associated transcriptional programs in GBM and to assess their functional relevance using integrative computational and experimental approaches.

Transcriptomic data from The Cancer Genome Atlas (TCGA)-GBM and Genotype-Tissue Expression (GTex) brain cortex were analyzed following batch correction, differential expression analysis, and gene ontology enrichment. TCGA-GBM samples were stratified into BORIS-high and BORIS-low expression quartiles to identify BORIS-associated gene signatures. BORIS chromatin occupancy was examined by Chromatin immunoprecipitation combined with sequencing (ChIP-seq) in U87MG cells, followed by functional annotation of BORIS-bound genes. Experimental validation included BORIS overexpression, RT-qPCR, immunoblotting, ChIP-qPCR, and functional assays assessing proliferation, clonogenic survival, and migration.

BORIS was significantly upregulated in GBM compared with normal brain tissue and was associated with transcriptional programs related to development, metabolism, and cell signaling. Quartile-based analysis identified BORIS-associated differentially expressed genes, including CD36 and FBN2. ChIP-seq revealed BORIS binding at promoter-proximal regions, with ChIP-qPCR confirming occupancy at CD36 and FBN2 regulatory regions. BORIS overexpression increased CD36 and FBN2 expression and was associated with reduced proliferation, enhanced clonogenic survival, and increased migratory capacity.

These findings indicate that BORIS is associated with transcriptional and phenotypic programs linked to GBM aggressiveness and may represent a candidate for further investigation as a biomarker or therapeutic target in GBM.