Fortin Bridget M, Mahieu Alisa L, Fellows Rachel C, Pannunzio Nicholas R, Masri Selma
Department of Biological Chemistry, University of California, Irvine, Irvine, California, 92697, USA.
Department of Medicine, University of California, Irvine, Irvine, California, 92697, USA.
F1000Res. 2023 May 16;12:116. doi: 10.12688/f1000research.128716.2. eCollection 2023.
In modern society, there is a growing population affected by circadian clock disruption through night shift work, artificial light-at-night exposure, and erratic eating patterns. Concurrently, the rate of cancer incidence in individuals under the age of 50 is increasing at an alarming rate, and though the precise risk factors remain undefined, the potential links between circadian clock deregulation and young-onset cancers is compelling. To explore the complex biological functions of the clock, this review will first provide a framework for the mammalian circadian clock in regulating critical cellular processes including cell cycle control, DNA damage response, DNA repair, and immunity under conditions of physiological homeostasis. Additionally, this review will deconvolute the role of the circadian clock in cancer, citing divergent evidence suggesting tissue-specific roles of the biological pacemaker in cancer types such as breast, lung, colorectal, and hepatocellular carcinoma. Recent evidence has emerged regarding the role of the clock in the intestinal epithelium, as well as new insights into how genetic and environmental disruption of the clock is linked with colorectal cancer, and the molecular underpinnings of these findings will be discussed. To place these findings within a context and framework that can be applied towards human health, a focus on how the circadian clock can be leveraged for cancer prevention and chronomedicine-based therapies will be outlined.
在现代社会，因夜班工作、夜间人工光照暴露和不规律饮食模式而受昼夜节律紊乱影响的人口正在增加。与此同时，50岁以下人群的癌症发病率正以惊人的速度上升，尽管确切的风险因素仍不明确，但昼夜节律失调与青年期癌症之间的潜在联系令人信服。为了探索生物钟的复杂生物学功能，本综述将首先提供一个关于哺乳动物生物钟在生理稳态条件下调节关键细胞过程（包括细胞周期控制、DNA损伤反应、DNA修复和免疫）的框架。此外，本综述将剖析生物钟在癌症中的作用，引用不同证据表明生物起搏器在乳腺癌、肺癌、结直肠癌和肝细胞癌等癌症类型中的组织特异性作用。关于生物钟在肠上皮中的作用，以及生物钟的基因和环境破坏与结直肠癌如何关联的新见解已经出现，将讨论这些发现的分子基础。为了将这些发现置于可应用于人类健康的背景和框架中，将概述如何利用昼夜节律进行癌症预防和基于时辰医学的治疗。
