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

Gerardo Ramírez-Mejía^1,#, Sofía Plata-Burgos^1,#, Raquel Cuevas-Díaz Duran², Adrian Ledesma-Beiza¹, Cynthia Sámano¹, Thalía Estefanía Sánchez-Correa³, Ernesto Soto-Reyes^1,*
1 Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa (UAM-C), Mexico City, Mexico
2 Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Mexico
3 Servicio de Neurocirugía, Hospital General Xoco, Mexico City, Mexico
* Corresponding Author: Ernesto Soto-Reyes. Email: email
# These authors contributed equally to this work as the first author
(This article belongs to the Special Issue: Cellular Mechanisms in Neurodegeneration, Injury, and Regeneration)

BIOCELL https://doi.org/10.32604/biocell.2026.075061

Received 24 October 2025; Accepted 14 January 2026; Published online 30 January 2026

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.