Carcinogenic efects of circadian disruption: an epigenetic viewpoint

Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, afects many biological processes within the body and results in diferent long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modiications and the formation of circadian epigenomes. Aberrant epigenetic modiications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic efects of circadian disruption. In this review, I irst discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modiications that result in circadian disruption. In addition, I explain the carcinogenic efects of circadian disruption and highlight its potential role in diferent human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.

The role of circadian rhythm in breast cancer

The circadian rhythm is an endogenous time keeping system shared by most organisms. The circadian clock is comprised of both peripheral oscillators in most organ tissues of the body and a central pacemaker located in the suprachiasmatic nucleus （SCN） of the central nervous system. The circadian rhythm is crucial in maintaining the normal physiology of the organism including, but not limited to, cell proliferation, cell cycle progression, and cellular metabolism; whereas disruption of the circadian rhythm is closely related to multi-tumorigenesis. In the past several years, studies from different fields have revealed that the genetic or functional disruption of the molecular circadian rhythm has been found in various cancers, such as breast, prostate, and ovarian. In this review, we will investigate and present an overview of the current research on the influence of circadian rhythm regulating proteins on breast cancer.

The role of circadian clocks in cancer:Mechanisms and clinical implications

Circadian rhythm refers to the inherent 24-h cycle oscillation of biochemical,phys-iological and behavioral functions,which is almost universal in eukaryotes.At least 14 core clock genes have been reported to form multiple chain feedback loops that confer intrinsic circadian rhythmicity onto the molecular clock.Accumulating evidence has shown that the circadian gene dysfunction resulted from single nucleotide polymorphisms(SNPs),deletions,epigenetic modification,and deregulation is strongly associated with cancer risk.In the pre-sent review,we describe the composition of circadian rhythm system.We highlight the func-tion and mechanism of clock genes in cancer pathogenesis and progression.Moreover,their potential clinical implications as prognostic biomarkers and therapeutic targets have been ad-dressed.

Circadian rhythm in prostate cancer: time to take notice of the clock

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment.Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers,including prostate cancer(PCa).Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa.This review begins with patterns of the circadian clock,highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels,and discusses possible new approaches to PCa therapy that target the circadian clock.

Circadian rhythm disruption and endocrine-related tumors

This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.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,infec-tions,and cancer.We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis.Specific associ-ations 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 microenvir-onment.We advocated for integrating biological timing into clinical consider-ations for personalized healthcare,proposing that understanding these connec-tions 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.

近日节律在肿瘤治疗中的应用进展

近日节律是生物生命活动的基本特征之一,它与肿瘤的发生、发展、转移和预后紧密相关,并影响抗癌药物的耐受性和疗效。研究近日节律与肿瘤的相关性,利于预防、诊断和治疗恶性肿瘤,提高患者存活率和生活质量。本研究就近日节律在肿瘤治疗中的应用作一综述,以期为近日节律的进一步研究奠定基础。

近日节律紊乱与癌症关系的研究进展

动物实验及流行病学研究结果表明,癌症的发生发展与近日节律的紊乱密切相关。目前关于近日节律紊乱与癌症关系的研究还存在一些局限性:人群流行病学研究目前主要是发现夜间倒班、跨时差飞行等所致的节律紊乱与乳腺癌、前列腺癌发病关系密切,而关于其它癌症的研究报道较少。虽然近日节律失调与癌症的关系已经得到证实,但其机制尚未确定,大多数学者认为,节律紊乱的致癌作用主要与褪黑素分泌的降低和生物钟基因表达的紊乱有关。

昼夜节律在皮肤生理和皮肤癌中的作用

昼夜节律是生物体生命的基本组成部分,使机体广泛的生理功能产生24 h规律波动。近年研究发现,皮肤的各种生理功能受昼夜节律调控,包括皮肤屏障功能、皮肤血流量和皮肤角质形成细胞增殖等。同时,由外界因素引起的昼夜节律紊乱与皮肤癌的发生发展有关。本文旨在从皮肤生理功能及皮肤癌的角度阐述昼夜节律与皮肤的研究进展,为今后皮肤癌的综合防治提供新思路。