Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Int J Urol. 2020 Jun;27(6):518-524. doi: 10.1111/iju.14231. Epub 2020 Mar 28.
The circadian clock controls and adapts diverse physiological and behavioral processes according to Earth's 24-h cycle of environmental changes. The master pacemaker of the mammalian circadian clock resides in the hypothalamic suprachiasmatic nucleus, but almost all cells throughout the body show circadian oscillations in gene expression patterns and associated functions. Recent studies have shown that the circadian clock gradually develops during embryogenesis. Embryonic stem cells and induced pluripotent stem cells do not show circadian oscillations of gene expression, but gradually develop circadian clock oscillation during differentiation; thus, the developmental program of circadian clock emergence appears closely associated with cellular differentiation. Like embryonic stem cells, certain cancer cell types also lack the circadian clock. Given this similarity between embryonic stem cells and cancer cells, interest is growing in the contributions of circadian clock dysfunction to dedifferentiation and cancer development. In this review, we summarize recent advances in our understanding of circadian clock emergence during ontogenesis, and discuss possible associations with cellular differentiation and carcinogenesis. Considering the multiple physiological functions of circadian rhythms, circadian abnormalities might contribute to a host of diseases, including cancer. Insights on circadian function could lead to the identification of biomarkers for cancer diagnosis and prognosis, as well as novel targets for treatment.
生物钟根据地球 24 小时的环境变化周期来控制和适应各种生理和行为过程。哺乳动物生物钟的主节奏起搏器位于下丘脑视交叉上核，但体内几乎所有细胞的基因表达模式和相关功能都表现出昼夜节律波动。最近的研究表明，生物钟在胚胎发生过程中逐渐发育。胚胎干细胞和诱导多能干细胞不表现出基因表达的昼夜节律波动，但在分化过程中逐渐发展出生物钟振荡；因此，生物钟出现的发育程序似乎与细胞分化密切相关。与胚胎干细胞类似，某些癌细胞类型也缺乏生物钟。鉴于胚胎干细胞和癌细胞之间存在这种相似性，人们越来越关注生物钟功能障碍对去分化和癌症发展的贡献。在这篇综述中，我们总结了我们对生物钟在个体发生过程中出现的理解的最新进展，并讨论了与细胞分化和癌变的可能关联。考虑到昼夜节律的多种生理功能，昼夜节律异常可能导致多种疾病，包括癌症。对生物钟功能的深入了解可能会为癌症的诊断和预后提供生物标志物，并为治疗提供新的靶点。
