昼夜节律是由涉及特定基因的分子钟系统在细胞水平上产生的。研究表明,生物钟中断是癌症进展的控制点。结直肠癌(CRC)是与昼夜节律紊乱密切相关的癌症之一。在本次审查中,总结了昼夜节律时钟在CRC发展中的作用.在CRC患者中发现了某些时钟基因的异常表达,并探讨了其与临床病理特征的相关性。周期和隐色2(Cry2),据报道Sirtuin1(SIRT1)和神经元PAS结构域蛋白2(NPAS2)基因具有肿瘤抑制特性。相反,Cry1,大脑和肌肉ARNT样1,昼夜节律运动输出周期kaput(CLOCK)和永恒可能会加剧CRC进展,但是这些发现并不一致,需要进一步的研究来证实。通过增加最大耐受剂量和降低毒性,昼夜节律时间表还表明在CRC患者的化疗治疗中具有优势。分子CLOCK系统的功能障碍破坏了细胞过程以加速结肠肿瘤发生,比如新陈代谢,细胞周期,DNA损伤修复,增殖和凋亡,上皮间质转化和干性。讨论了时钟基因网络以及系统的动力学如何影响CRC。
The circadian rhythm is generated at the cellular level by a molecular clock system that involves specific genes. Studies have revealed that circadian clock disruption is a control point in cancer progression. Colorectal cancer (CRC) is one of the cancers closely associated with circadian disruption. In the present
review, the involvement of the circadian clock in CRC development was summarized. Abnormal expression of certain clock genes has been found in patients with CRC and their correlation with clinicopathological features has also been explored. The period and cryptochrome 2 (Cry2), Sirtuin1 (SIRT1) and neuronal PAS domain protein 2 (NPAS2) genes were reported to have tumour suppressor properties. Conversely, Cry1, brain and muscle ARNT‑like‑1, circadian locomotor output cycles kaput (CLOCK) and timeless may aggravate CRC progression, but these findings are not consistent and require to be confirmed by further research. Circadian scheduling also indicated advantages in chemotherapy treatments for patients with CRC by increasing the maximum tolerated doses and decreasing toxicities. Dysfunction of the molecular CLOCK system disrupted cellular processes to accelerate colon tumorigenesis, such as metabolism, cell cycle, DNA damage repair, proliferation and apoptosis, epithelial‑mesenchymal transition and stemness. The clock gene network and how the dynamics of the system influence CRC were discussed.