By: Noah Beattie-Moss
The circadian rhythm, a 24-hour oscillation of physiological processes based on the day/night cycle, is vital for maintaining homeostasis of the body. Long-term disruption of this rhythm can have serious side-effects, as it has been implicated in tumorgenesis and cancer development. Women who work night shifts have been shown to have a moderate increase in breast cancer rates, and circadian disruption has been tied to liver carcinogenesis in mice models. The biological reasons for these connections have been largely unknown, but recent research published in the journal Cancer Cell may shed new light on the issue.
The study, led by Loning Fu of the Baylor College of Medicine in Houston, TX, compared mice under “chronic jet-lagged conditions” with mice with normal 24-hour cycles. The jet-lagged mice had significantly higher cancer rates, especially of hepatocellular carcinoma (HCC). HCC was also discovered earlier in jet-lagged mice, indicating that cancer progression was increased as well.
Analysis of gene expression in jet-lagged mice revealed genome-wide deregulation of many genes that are also deregulated in HCC. This included overexpression of several genes involved in regulating the circadian cycle of the liver, as well as upregulation of transcription factors involved in cell proliferation. It also causes elevated levels of bile acids, which activate CAR, a receptor which can cause non-alcoholic fatty liver disease (NAFLD), which leads to HCC. This pathway is also found in individuals with obesity, who are at a much higher risk for liver cancer compared to the general population.
Cancer rates have been on the rise, a phenomenon often attributed to lifestyle and environmental factors. This research provides definite insight into the mechanism by which circadian rhythm disruption acts as a risk factor for HCC. This pathway could potentially be a target for new cancer therapies which would restore bile acid homeostasis or inhibiting CAR, thus preventing the metabolic syndromes that are precursors to cancer.