Epigenetic Basis of Circadian Rhythm Disruption in Cancer

Self-sustained and synchronized to environmental stimuli, circadian clocks are under genetic and epigenetic regulation. Recent findings have greatly increased our understanding of epigenetic plasticity governed by circadian clock. Thus, the link between circadian clock and epigenetic machinery is reciprocal. Circadian clock can affect epigenetic features including genomic DNA methylation, noncoding RNA, mainly miRNA expression, and histone modifications resulted in their 24-h rhythms. Concomitantly, these epigenetic events can directly modulate cyclic system of transcription and translation of core circadian genes and indirectly clock output genes. Significant findings interlocking circadian clock, epigenetics, and cancer have been revealed, particularly in breast, colorectal, and blood cancers. Aberrant methylation of circadian gene promoter regions and miRNA expression affected circadian gene expression, together with 24-h expression oscillation pace have been frequently observed.