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SPATIOTEMPORAL DISTRIBUTION OF CIRCADIAN CLOCK PROTEINS AND THEIR IMPACT ON GENE EXPRESSION IN GLIOBLASTOMA <EM>IN VITRO</EM> MODELS
Emely Maqueda-Martínezand 4 co-authors
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS01-07AM-677
Presentation
Date TBA
Board: PS01-07AM-677
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Poster Board
PS01-07AM-677
Poster
View posterAbstract
Glioblastoma (GB) is a highly aggressive malignant brain tumor characterized by heterogeneity and poor prognosis. Recent evidence suggests that while the endogenous 24-hour circadian clock remains functional in GB, it undergoes a "gain of control" over specific genes promoting tumor progression and maintaining glioblastoma stem-like cells (GSLCs).
This study examines the spatiotemporal distribution of clock proteins CLOCK, BMAL1, PER2, and CRY1 and their role in oscillatory gene expression in GB models. Using U87 cells synchronized via serum shock, gene expression was monitored through qRT-PCR, while protein distribution was evaluated using 3D confocal microscopy. Rhythmic transcription was observed for BMAL1, DBP, and PER2.
Analysis of public GSLC ChIP-seq data revealed tissue-specific BMAL1 binding. While neural stem like cells showed 74,656 exclusive peaks, GSLCs exhibited 18,536 exclusive peaks, 70% of which were in promoter regions. These gained regions were enriched in promoters of factors associated with stemness and poor prognosis, such as NRF1, SOX3, and SMAD4. These findings suggest the GB molecular clock influences transcriptional regulation and chromatin structure of non-canonical genes, highlighting the potential for chronotherapy to disrupt malignancy.
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