Implications of Circadian Rhythm Regulation by microRNAs in Colorectal Cancer

AIM: To establish a connection between microRNA (miRNAs), circadian rhythm, and colorectal cancer patient survival. METHODS: Genomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) colorectal cancer database, and the expression levels of candidate miRNAs and a set of circadian rhythm-related genes (Per1, Per2, Per3, Bmal1), and genes associated with chemosensitivity (thymidylate synthase, dihydrofolate reductase) were assessed for any correlations among their expression. In addition, survival analyses specific to different colorectal cancer stages were performed to determine if these genes contribute to patient outcomes. RESULTS: Significant inverse correlation between the expression of Per1 and that of miR-192 and miR-194 was observed. In survival analyses, high miR-192 and miR-194 correlate with better overall survival in Stage II patients, but worse survival in more advanced Stage III/IV patients. The expression of Per1, but Per2 or Bmal1, is marginally associated with patient survival for Stage II patients. Low thymidylate synthase expression correlates with better overall survival in Stage II patients but worse survival in Stage III/IV patients. CONCLUSION: This study establishes a foundation based on a large genomic database of colorectal cancer, for further investigation into the importance of regulatory mechanisms of circadian rhythm by miRNAs in colorectal cancer.