Biological clock regulation by the PER gene family: a new perspective on tumor development

Chen, Kai; Wang, Yaohui; Li, Dengxiong; Wu, Ruicheng; Wang, Jie; Wei, Wuran; Zhu, Wei; Xie, Wenhua; Feng, Dechao; He, Yi

doi:10.3389/fcell.2024.1332506

Cited by 2 publications

(3 citation statements)

References 179 publications

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Section: Prognostic Value For Circadian Clock Genes In Cancer Diagnosismentioning

confidence: 99%

“…Circadian CGs, particularly the PER gene family, play a crucial role in cancer progression and patient prognosis[ 194 ]. Mutations in these genes can affect cell function, metabolism, immunity, and response to treatment, contributing to varying cancer outcomes[ 194 , 195 ]. Studies have shown that the expression levels of circadian genes are significantly altered in cancers such as colorectal carcinoma, HER2-positive advanced gastric cancer, BC, pancreatic cancer, and obesity-related cancers[ 196 - 200 ].…”

Section: Prognostic Value For Circadian Clock Genes In Cancer Diagnosismentioning

confidence: 99%

“…In BC, disruptions in circadian rhythms and alterations in circadian gene expression have been linked to different BC subtypes, tumor progression, and response to chemotherapy and radiotherapy[ 196 , 203 - 205 ]. Notably, lower expression of PER genes has been correlated with more aggressive tumor phenotypes and poorer survival rates in some cases[ 194 , 202 ], whereas in adrenocortical carcinoma PER1 expression is enhanced[ 155 ] and in pituitary adenomas there is marked overexpression of Per2 [ 176 ]. It is evident that different types of tumors display distinct alterations in CGs that could be associated with prognosis and survival rates.…”

Section: Prognostic Value For Circadian Clock Genes In Cancer Diagnosismentioning

confidence: 99%

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Circadian rhythm disruption and endocrine-related tumors

Savvidis,

Kallistrou,

Kouroglou

et al. 2024

World J Clin Oncol

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This review delved into the intricate relationship between circadian clocks and physiological processes, emphasizing their critical role in maintaining homeostasis. Orchestrated by interlocked clock genes, the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle, energy metabolism, immune function, and cell proliferation. The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles, while peripheral tissue clocks are influenced by cues such as feeding times. Circadian disruption, linked to modern lifestyle factors like night shift work, correlates with adverse health outcomes, including metabolic syndrome, cardiovascular diseases, infections, and cancer. We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis. Specific associations between circadian disruption and endocrine tumors, spanning breast, ovarian, testicular, prostate, thyroid, pituitary, and adrenal gland cancers, are highlighted. Shift work is associated with increased breast cancer risk, with PER genes influencing tumor progression and drug resistance. CLOCK gene expression correlates with cisplatin resistance in ovarian cancer, while factors like aging and intermittent fasting affect prostate cancer. Our review underscored the intricate interplay between circadian rhythms and cancer, involving the regulation of the cell cycle, DNA repair, metabolism, immune function, and the tumor microenvironment. We advocated for integrating biological timing into clinical considerations for personalized healthcare, proposing that understanding these connections could lead to novel therapeutic approaches. Evidence supports circadian rhythm-focused therapies, particularly chronotherapy, for treating endocrine tumors. Our review called for further research to uncover detailed connections between circadian clocks and cancer, providing essential insights for targeted treatments. We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.

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Section: Prognostic Value For Circadian Clock Genes In Cancer Diagnosismentioning

confidence: 99%

Section: Prognostic Value For Circadian Clock Genes In Cancer Diagnosismentioning

confidence: 99%

Section: Prognostic Value For Circadian Clock Genes In Cancer Diagnosismentioning

confidence: 99%

See 1 more Smart Citation

Circadian rhythm disruption and endocrine-related tumors

Savvidis,

Kallistrou,

Kouroglou

et al. 2024

World J Clin Oncol

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Impact of Circadian Clock PER2 Gene Overexpression on Rumen Epithelial Cell Dynamics and VFA Transport Protein Expression

Ali,

Zhen,

Zanna

et al. 2024

IJMS

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The circadian gene PER2 is recognized for its regulatory effects on cell proliferation and lipid metabolism across various non-ruminant cells. This study investigates the influence of PER2 gene overexpression on goat rumen epithelial cells using a constructed pcDNA3.1-PER2 plasmid, assessing its impact on circadian gene expression, cell proliferation, and mRNA levels of short-chain fatty acid (SCFA) transporters, alongside genes related to lipid metabolism, cell proliferation, and apoptosis. Rumen epithelial cells were obtained every four hours from healthy dairy goats (n = 3; aged 1.5 years; average weight 45.34 ± 4.28 kg), cultured for 48 h in vitro, and segregated into control (pcDNA3.1) and overexpressed (pcDNA3.1-PER2) groups, each with four biological replicates. The study examined the potential connection between circadian rhythms and nutrient assimilation in ruminant, including cell proliferation, apoptosis, cell cycle dynamics, and antioxidant activity and the expression of circadian-related genes, VFA transporter genes and regulatory factors. The introduction of the pcDNA3.1-PER2 plasmid drastically elevated PER2 expression levels by 3471.48-fold compared to controls (p < 0.01), confirming effective overexpression. PER2 overexpression resulted in a significant increase in apoptosis rates (p < 0.05) and a notable reduction in cell proliferation at 24 and 48 h post-transfection (p < 0.05), illustrating an inhibitory effect on rumen epithelial cell growth. PER2 elevation significantly boosted the expression of CCND1, WEE1, p21, and p16 (p < 0.05) while diminishing CDK4 expression (p < 0.05). While the general expression of intracellular inflammation genes remained stable, TNF-α expression notably increased. Antioxidant marker levels (SOD, MDA, GSH-Px, CAT, and T-AOC) exhibited no significant change, suggesting no oxidative damage due to PER2 overexpression. Furthermore, PER2 overexpression significantly downregulated AE2, NHE1, MCT1, and MCT4 mRNA expressions while upregulating PAT1 and VH+ ATPase. These results suggest that PER2 overexpression impairs cell proliferation, enhances apoptosis, and modulates VFA transporter-related factors in the rumen epithelium. This study implies that the PER2 gene may regulate VFA absorption through modulation of VFA transporters in rumen epithelial cells, necessitating further research into its specific regulatory mechanisms.

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Biological clock regulation by the PER gene family: a new perspective on tumor development

Cited by 2 publications

References 179 publications

Circadian rhythm disruption and endocrine-related tumors

Circadian rhythm disruption and endocrine-related tumors

Impact of Circadian Clock PER2 Gene Overexpression on Rumen Epithelial Cell Dynamics and VFA Transport Protein Expression

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