The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development

Jan 17, 2025Cell communication and signaling : CCS

The role of daily body clock proteins in stress from oxidation, immune response, and cancer development

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Abstract

The PERIOD proteins () significantly influence physiological processes, including and immune functionality.

PER proteins are crucial for regulating the circadian clock, affecting various physiological and behavioral processes.
PER1 interacts with GPX1 to coordinate mitochondrial dynamics and energy management in relation to daily rhythms.
In innate immune cells, PERs affect the activity patterns of inflammatory markers NF-κB and TNF-α, influencing responses to toxic shock.
PERs can alter cancer cell behaviors, impacting proliferation, apoptosis, and migration through oncogene expression.
PER2 and PER3 act as antagonists in cancer stem cell biology, influencing differentiation and maintenance of stemness.
The expression levels of PERs may serve as significant indicators for early cancer diagnosis and prognosis.

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The complex interaction between and physiological functions is essential for maintaining human health. At the heart of this interaction lies the PERIOD proteins (), pivotal to the circadian clock, influencing the timing of physiological and behavioral processes and impacting , immune functionality, and tumorigenesis. PER1 orchestrates the cooperation of the enzyme GPX1, modulating mitochondrial dynamics in sync with daily rhythms and oxidative stress, thus regulating the mechanisms managing energy substrates. PERs in innate immune cells modulate the temporal patterns of NF-κB and TNF-α activities, as well as the response to LPS-induced toxic shock, initiating inflammatory responses that escalate into chronic inflammatory conditions. Crucially, PERs modulate cancer cell behaviors including proliferation, apoptosis, and migration by influencing the levels of cell cycle proteins and stimulating the expression of oncogenes c-Myc and MDM2. PER2/3, as antagonists in cancer stem cell biology, play important roles in differentiating cancer stem cells and in maintaining their stemness. Importantly, the expression of Pers serve as a significant factor for early cancer diagnosis and prognosis. This review delves into the link between circadian rhythm regulator PERs, disruptions in circadian rhythm, and oncogenesis. We examine the evidence that highlights how dysfunctions in PERs activities initiate cancer development, aid tumor growth, and modify cancer cell metabolism through pathways involved in oxidative stress and immune system. Comprehending these connections opens new pathways for the development of circadian rhythm-based therapeutic strategies, with the aims of boosting immune responses and enhancing cancer treatments.

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The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development

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