Role of the period family in mediating the interplay between circadian disruption and cancer (Review)

Abstract

The circadian clock, which is based on 24-h cyclical changes in the external environment, can be detected in almost all cells and regulates several vital physiological processes. The circadian rhythm is disrupted in numerous individuals for several reasons, such as shift work, chronic jet lag, high fat intake and abnormal sleep patterns. Disruption of the circadian rhythm can increase the risk of cancer, affecting its development and treatment. The Period gene family is a core component of the circadian rhythm cycle, and the mechanisms by which its changes affect cancer progression are unclear. The present study reviewed the current research on the intricate relationship between disruption of the circadian clock, particularly focusing on the Period gene family, and its effect on the occurrence, progression and therapeutic approaches for cancer.

Keywords: cancer; circadian clock; circadian rhythms; clock gene period.

Figure 1.

Circadian feedback loop and its correlation with cancer. (A) Nighttime light, waking up at night and eating late at night can increase the susceptibility to cancer. Morning and evening activity can reduce cancer susceptibility. (B) Circadian transcriptional and translational feedback loop machinery in mammals. PER, period circadian regulator; CRY, circadian regulator; BMAL1, basic helix-loop-helix ARNT like 1; CLOCK, heterodimeric clock circadian regulator; RORs, RAR related orphan receptor; REV-ERB, nuclear receptor subfamily 1 group D member 1; NFIL3, nuclear factor, interleukin 3 regulated; DBP, D-box binding PAR BZIP transcription factor.

Figure 2.

Mechanisms by which PER inhibits tumors. The PER gene interacts with various cancer-related genes and pathways to influence the development of cancer. miR, microRNA; PER, period circadian regulator; p53, protein 53; ALKBH5, AlkB homolog 5; m6A, N6-methyladenosine; YTHDF2, YT521-B homology domain family 2; CDKs, cyclin-dependent kinases; CKIs, CDK inhibitors; HIF1α, hypoxia-inducible factor 1α; Aldh3a1, aldehyde dehydrogenase 3 family, A member 1; KMT2D, lysine-specific methyltransferase 2D; SREBP1c, sterol regulatory element-binding protein 1c; UV, ultraviolet; MDM2, MDM2 proto-oncogene; ZNF704, zinc finger protein 704; SIN3A, SIN3 transcription regulator family member A; OCT1, POU class 2 homeobox 1; Bid, BH3-interacting domain death agonist.