Circadian Clock and Liver Cancer

Abstract

Circadian clocks control several homeostatic processes in mammals through internal molecular mechanisms. Chronic perturbation of circadian rhythms is associated with metabolic diseases and increased cancer risk, including liver cancer. The hepatic physiology follows a daily rhythm, driven by clock genes that control the expression of several proteins involved in distinct metabolic pathways. Alteration of the liver clock results in metabolic disorders, such as non-alcoholic fatty liver diseases (NAFLD) and impaired glucose metabolism, that can trigger the activation of oncogenic pathways, inducing spontaneous hepatocarcinoma (HCC). In this review, we provide an overview of the role of the liver clock in the metabolic and oncogenic changes that lead to HCC and discuss new potentially useful targets for prevention and management of HCC.

Nuclear receptors: a bridge linking the gut microbiome and the host

“…Moreover, the gut microbiome could mediate PPARγ-driven liver circadian clock reprogramming (Murakami et al 2016). The hepatic physiology follows a daily rhythm and the perturbation of the liver clock results in metabolic disorders such as NAFLD (Crespo et al 2021) and even liver cancer (Mazzoccoli et al 2019) through regulating rhythm gene expression and the rhythm-related signaling pathways. Thus, the gut microbiome-PPARγ axis may mediate the circadian clock to affect liver diseases such as NAFLD and cancer.…”

An Analysis of Microwave Ablation Parameters for Treatment of Liver Tumors from the 3D-IRCADb-01 Database

“…Liver cancer, also known as hepatic cancer, arises because of the abnormal growth of cells inside the liver [ 1 , 2 , 3 , 4 , 5 ]. It may originate in the liver from hepatocytes, bile duct epithelium, or mesenchymal tissue (primary) or spread to the liver from primary cancer developed elsewhere in the body (secondary) [ 6 , 7 , 8 , 9 , 10 ].…”

Circadian Rhythm Dysregulation and Leukemia Development: The Role of Clock Genes as Promising Biomarkers

“…In the early hours of dawn, even with the binding of the CLOCK-BMAL1 complex in its target E-box sequence, the high levels of CRY and PER bind to this complex and inhibit their transcription, creating the repressive regulation [ 34 ]. Consequently, CRY and PER repress their own expression, and by the sunrise, the lack of production of CRY and PER proteins causes reduced levels in the cell nucleus and, in the absence of binding to CLOCK-BMAL1, allows these complexes to start their transcription, creating the active regulation [ 8 , 34 ]. In the early evening, due to the high expression of CG throughout the day, the levels of CRY and PER rise again; in this way, they manage to enter the nucleus by binding with casein kinase 1 epsilon (CK1ε), constituting the PER-CRY-CK1ε complex, and they suppress the positive transcription of CLOCK-BMAL1, thus restarting another cycle ( Figure 1 ) [ 35 ].…”

“…For the control, the activation and repression of CC genes may need environmental stimuli—known as zeitgebers (ZTGBs)—which can be a photic or a non-photic stimulus, where the most studied are the photic stimuli, or the light/dark cycle [ 6 , 7 ]. They are accountable for sending signals to the suprachiasmatic nucleus (SCN) in the central nervous system, stimulating CG transcription located in peripheral tissues, and promoting cell metabolic functions [ 8 ].…”