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 implic...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.Quartilebased 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.展开更多
基金supported by the Secretaría de Ciencia,Humanidades,Tecnología e Innovación(SECIHTI),Fondo Ciencia Básica y de Frontera 2025(CBF-2025-G-97)to E.Soto-Reyes and PRODEP(511/2023-3066-1599)SECIHTI,Fondo de Ciencia de Frontera 2023(CF-2023-G398)to C.Sámano+2 种基金supported by the Departamen to de Ciencias Naturales(DCN),División de Ciencias Naturales e Ingeniería(DCNI),UAM,Unidad Cuajimalpa,through Divisional Project Number 101S243-23 to E.Soto-Reyes and 123 S289-25 to C.Sámanoa master student from Programa de Maestría y Doctorado en Ciencias Bio-químicas,Universidad Nacional Autónoma deMéxico(UNAM)and received a fellowship(CVU number 1184475)fromSecretaría de Ciencia,Humanidades,Tecnología e Innovación(SECIHTI),Mexicoa postdoctoral fellow at the Universidad Autónoma Metropolitana-Cuajimalpa(UAM-C)and received a fellowship(CVU number 588333)from SECIHTI,Mexico.
文摘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.Quartilebased 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.
