Han Yuyan, Chen Lixian, Baiocchi Leonardo, Ceci Ludovica, Glaser Shannon, Francis Heather, Alpini Gianfranco, Kennedy Lindsey
School of Biological Sciences, University of Northern Colorado, Greeley, CO.
Hepatology and Gastroenterology, Medicine, Indiana University School of Medicine, Indianapolis, IN.
Crit Rev Oncog. 2021;26(3):69-85. doi: 10.1615/CritRevOncog.2021039881.
Liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, can be devastating if not treated early. The risk factors of liver cancer include alcoholic liver disease, non-alcoholic fatty liver disease, disruption of melatonin levels, and dysregulated circadian rhythm. The circadian rhythm is a 24-hour biological clock that regulates the physiological activities at both central and peripheral levels. Its molecular mechanism exists in every cell in mammals. Disruption of the circadian rhythm has found in liver cancers as an independent risk factor. This review summarized the most recent findings about the molecular mechanisms of circadian rhythm, the crosstalk between core clock genes and melatonin, as well as the role of circadian rhythm and melatonin played in chronic liver diseases and liver cancer. Finally, we discussed the potential clinical application of circadian rhythm and melatonin for the treatment of liver cancer and discussed future perspectives of how understanding the circadian rhythm in liver cancer progression could provide new clinical applications for liver cancer treatment and diagnosis.
肝癌，包括肝细胞癌和胆管癌，如果不及早治疗，可能会造成严重后果。肝癌的风险因素包括酒精性肝病、非酒精性脂肪性肝病、褪黑素水平紊乱和昼夜节律失调。昼夜节律是一个24小时的生物钟，在中枢和外周水平调节生理活动。其分子机制存在于哺乳动物的每个细胞中。昼夜节律失调已被发现是肝癌的一个独立风险因素。这篇综述总结了关于昼夜节律分子机制、核心生物钟基因与褪黑素之间的相互作用，以及昼夜节律和褪黑素在慢性肝病和肝癌中所起作用的最新研究结果。最后，我们讨论了昼夜节律和褪黑素在肝癌治疗中的潜在临床应用，并探讨了了解肝癌进展中的昼夜节律如何为肝癌治疗和诊断提供新的临床应用的未来前景。
