Research progress on the role of circadian clock genes in the occurrence and development of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) stands as the primary cause of cancer-related death globally, being characterized by a complex interaction of genetic, epigenetic, and environmental factors. Circadian rhythm is the internal timekeeping mechanism that aligns an organism's physiological and behavioral patterns with the 24-hour day-night cycle. The dysregulation of circadian clock genes is closely linked to the pathogenesis of HCC. The molecular mechanism of HCC is complex and multifactorial. This review reviews the expression and function of CLOCK genes including BMAL1, clock, PER2, CRY1, CRY2, NPAS2, Timeless, NR1D1, NR1D2 and CSNK1D in HCC. The review argues how dysregulation of these genes leads to abnormal cell cycle control, impaired apoptosis, and altered metabolism, which are hallmarks of HCC, and also covers epigenetic modifications and non-coding RNA that regulate the expression of genes in liver cancer circadian rhythms. This review discusses the current understanding of the role of different types of circadian rhythm genes in cancer risk and progression. And the idea of using the circadian system "chronotherapy" as a potential treatment. Further research into the underlying mechanisms of HCC circadian rhythms is warranted and may lead to the innovative approaches in cancer prevention and treatment.