PDF(Pubmed)
Abstract：
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.
摘要：
这篇综述深入研究了生物钟与生理过程之间的复杂关系，强调它们在维持体内平衡方面的关键作用。由互锁的时钟基因编排，昼夜节律计时系统调节基本过程，如睡眠-觉醒周期，能量代谢，免疫功能，和细胞增殖。下丘脑视交叉上核的中心振荡器与明暗周期同步，而外周组织时钟受到诸如进食时间等线索的影响。昼夜节律中断，与夜班工作等现代生活方式有关，与不良健康结果相关，包括代谢综合征,心血管疾病,感染,和癌症。我们探讨了生物钟基因的分子机制及其对代谢紊乱和癌症发病机制的影响。昼夜节律紊乱和内分泌肿瘤之间的特定关联，跨越乳房，卵巢,睾丸,前列腺,甲状腺，垂体,和肾上腺癌，被突出显示。轮班工作与乳腺癌风险增加有关，PER基因影响肿瘤进展和耐药性。CLOCK基因表达与卵巢癌顺铂耐药相关,而衰老和间歇性禁食等因素会影响前列腺癌。我们的评论强调了昼夜节律和癌症之间复杂的相互作用，涉及细胞周期的调节，DNA修复,新陈代谢，免疫功能，和肿瘤微环境。我们提倡将生物定时整合到个性化医疗保健的临床考虑中，提出理解这些联系可能会导致新的治疗方法。证据支持以昼夜节律为中心的疗法，尤其是时间疗法，用于治疗内分泌肿瘤。我们的评论呼吁进一步研究以揭示生物钟与癌症之间的详细联系，为靶向治疗提供必要的见解。我们强调了公共卫生干预措施对减轻与生活方式相关的昼夜节律干扰的重要性，并强调了昼夜节律在疾病机制和治疗干预中的关键作用。
