Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Circadian Gene cry Controls Glioblastoma Tumorigenesis through Modulation of myc Expression

Version 1 : Received: 1 December 2021 / Approved: 2 December 2021 / Online: 2 December 2021 (09:30:17 CET)

How to cite: Jarabo, P.; de Pablo, C.; González-Blanco, A.; Casas-Tintó, S. Circadian Gene cry Controls Glioblastoma Tumorigenesis through Modulation of myc Expression. Preprints 2021, 2021120023 (doi: 10.20944/preprints202112.0023.v1). Jarabo, P.; de Pablo, C.; González-Blanco, A.; Casas-Tintó, S. Circadian Gene cry Controls Glioblastoma Tumorigenesis through Modulation of myc Expression. Preprints 2021, 2021120023 (doi: 10.20944/preprints202112.0023.v1).

Abstract

Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. It is a very aggressive tumor that grows fast and spreads through the brain causing the death of patients in 15 months. GB cells mutate frequently and generate a heterogeneous population of tumoral cells genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We use a Drosophila model of GB that reproduces the features of human GB, and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We study the contribution of cry to the expansion of GB cells, to the neurodegeneration caused by GB, and to premature death and determine that cry is required for GB progression. Moreover, we analyze the mechanisms that regulate cry expression by the PI3K pathway. Finally, we conclude that cry is necessary and sufficient to regulate myc expression in GB. These results contribute to the understanding of the signals that impulse GB malignancy and lethality and open novel opportunities for the treatment of GB patients.

Keywords

Cancer; neurodegeneration; glioma; Drosophila; disease model; PI3K; EGFR; genetics

Subject

LIFE SCIENCES, Genetics

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