**2. The relationship between transcriptional regulation of oncogenes and circadian clocks**

The disruption of circadian clocks can have a profound effect on animal health and is linked to abnormal development and cancer [6, 9]. Expression of the circadian clock genes has been reported to be dysregulated in human cancers [12]. The circadian transcriptional machinery, cellular clock, has been reported to control expression of tumor suppressors. Thus, the abnormal control of clock genes' expression in cancer cells activates oncogenic signaling pathways by functional inhibition of tumor suppressors, such as ataxia telangiectasia mutated (ATM), p53, p21, and WEE1 [12].

The Wingless-related integration site (Wnt) signaling pathways collectively play important roles in developmental, proliferative, and cell death processes [13]. Mutations in genes encoding the various components of Wnt pathways have been identified that contribute to various types of cancer including hepatocellular carcinoma, pancreatic tumors, ovarian cancer, and breast cancer. Importantly, there are several lines of evidence that suggest the existence of an interaction between circadian clocks and Wnt signaling pathways. Previous study have performed microarray-based screening for circadian genes in several mouse tissues and have constructed a publicly accessible database, by which users can query for finding circadianly regulated genes or for the study of the temporal expression patterns of their genes of interest [14]. Interestingly, in this database, several Wnt signaling pathway genes, such as *Axin2*, *Frizzled3* (*Fzd3*), and *Disheveled* (*Dvl1*), show a circadian pattern of expression, suggesting the possibility that circadian clocks control transcription of Wnt signaling pathway genes. The future study of the connecting routes that link the circadian transcriptional machinery to Wnt signaling pathway will reveal a molecular link between circadian clock deficiency and tumorigenesis.
