Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
School of Life Sciences, Coventry University, Alison Gingell Building Room 2.24, Coventry, CV1 5FB, UK.
IUBMB Life. 2019 Jul;71(7):771-780. doi: 10.1002/iub.2005. Epub 2019 Jan 23.
The circadian clock and the ~24 h rhythms it generates are essential in maintaining regular tissue functioning. At the molecular level, the circadian clock comprises a core set of rhythmically expressed genes and gene products that are able to drive rhythmic expression of other genes to generate overt circadian rhythms. It has recently come to light that perturbations of circadian rhythms contribute to the development of pathological states such as cancer, and altered expression and/or regulation of circadian clock genes has been identified in multiple tumour types. This review summarises the important role the circadian system plays in regulating cellular processes, including the cell cycle, apoptosis, DNA repair, the epithelial-to-mesenchymal transition, metabolism and immunity and how its dysregulation has widespread implications and could be a critical player in the development of cancer. Understanding its role in cancer development is important for the field chronotherapy, where the timing of chemotherapy administration is optimised based on differences in circadian clock functioning in normal and cancer cells. This has been found to influence the patient response, minimising the side effects commonly associated with chemotherapy. © 2019 IUBMB Life, 2019.
生物钟及其产生的约 24 小时节律对于维持组织的正常功能至关重要。从分子水平上讲,生物钟由一组节律性表达的基因和基因产物组成,这些基因和基因产物能够驱动其他基因的节律性表达,从而产生明显的昼夜节律。最近发现,昼夜节律的紊乱会导致癌症等病理状态的发展,并且在多种肿瘤类型中已经发现了生物钟基因的表达和/或调节改变。本文综述了生物钟系统在调节细胞过程中的重要作用,包括细胞周期、细胞凋亡、DNA 修复、上皮-间充质转化、代谢和免疫,以及其失调如何产生广泛的影响,并可能成为癌症发展的关键因素。了解生物钟在癌症发展中的作用对于时间治疗学领域很重要,该领域根据正常细胞和癌细胞中生物钟功能的差异来优化化疗药物的给药时间。这被发现会影响患者的反应,最大限度地减少与化疗相关的常见副作用。©2019 IUBMB Life,2019。