Clinical cancer epigenetics

in vitro experiments, we used the U87 MG glioblastoma cell line as our experimental platform.In our in vivo studies, we design two novel zebrafish (Danio rerio) models: the first model employs a constitutive KO that targets both CLOCK isoforms (Clocka and Clockb), while the second uses Cytosine Base Editing (CBE) to specifically disrupt CLOCK's epigenetic regulatory functions without interfering with its circadian role. ResultsIn the U87 MG CLOCK KO cell line, we observed a significant reduction in tumour cell aggressiveness, characterized by decreased proliferation and migration, as determined by the MTT assay, which was also confirmed by xenograft in zebrafish larvae.These findings emphasize the critical role of CLOCK in glioblastoma malignancy.The in vivo zebrafish models are designed to investigate the epigenetic CLOCK mechanisms involved in glioblastoma progression, particularly in existing zebrafish models of glioblastoma, such as P53-/-and NF1a-/-.Conclusions These preliminary results support the literature, which shows that CLOCK is upregulated in glioma tissues and is associated with increased proliferation, survival and migration.Our results suggest that KO models of CLOCK provide new insights into the mechanisms underlying tumour progression, suggesting the possibility of novel treatments.By disrupting the epigenetic functions of CLOCK, this research opens the way for innovative therapeutic approaches aimed at reducing the aggressiveness of glioblastoma and improving patient outcomes.