Metabolic Dysregulation and Circadian Clock in Cellular Models of Neuroendocrine Tumors

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Introduction: The circadian clock genes encode transcription factors whose interaction with nuclear receptors allows the regulation of cellular metabolism.The invalidation of the genes of the clock core is associated with the development of many endocrine diseases including neuroendocrine cancer. Recently, the family of transcriptional coactivators PGC-1a has been identified as a key element in the integration of cellular metabolic state with the circadian clock. PRC, as a member of the PGC-1 family, was able to interact with several transcription factors, including the CLOCK factor. The specific induction of this PRC factor by the cell cycle, to modulate the energy function, the MAPkinase pathway and the expression of microRNAs, makes it a key factor in the metabolic adaptation of cancer cells.

Aim(s): The PRC / CLOCK interaction would then reveal the role of the circadian clock both as a sensor and a mediator of the intracellular metabolic state particularly modified in neuroendocrine tumor cells.

Materials and methods: We have explored the regulation of energy metabolism in the context of circadian changes and proliferative status studying transcriptomic and epigenetic (acetylation, methylation, miRNA) profiles of three endocrine and neuroendocrine tumor cell lines with different PGC-1a / PRC expression ratios in relation to their metabolic profile and possibly invalidated for PRC, PGC -1a and CLOCK.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Savagner F

Authors: Savagner F, Le Pennec S,

Keywords: Metabolism, Circadian clock, cell models,