Disruption of clock gene expression in human colorectal liver metastases

AbstractThe circadian timing system controls about 40  % of the transcriptome and is important in the regulation of a wide variety of biological processes including metabolic and proliferative functions. Disruption of the circadian clock could have significant effect on human health and has an important role in the development of cancer. Here, we comp ared the expression levels of core clock genes in primary colorectal cancer (CRC), colorectal liver metastases (CRLM), and liver tissue within the same patient. Surgical specimens of 15 untreated patients with primary CRC and metachronous CRLM were studied. Quantitative real-time polymerase chain re action (qRT-PCR) was used to measure the expression of 10 clock genes:CLOCK,BMAL1,PER1,PER2,PER3,CRY1,CRY2,CSNK1E,TIM,TIPIN, and 2 clock-controlled genes:Cyclin-D1, andWEE1. Expression levels of 7 core clock genes were downregulated in CRLM:CLOCK (p = 0.006),BMAL1 (p = 0.003),PER1 (p = 0.003),PER2 (p = 0.002),PER3 (p <  0.001),CRY1 (p = 0.002), andCRY2 (p <  0.001). In CRC, 5 genes were downregulated:BMAL1 (p = 0.02),PER1 (p = 0.004),PER2 (p = 0.008),PER3 (p <  0.001), andCRY2 (p <  0.001).CSNK1E was upregulated in CRC (p = 0.02).Cyclin-D1 andWEE1 were both downregulated in CRLM and CRC. Related to clinicopathological factors, a significant correlation was found between low expression ofCRY1 and female gender, and lowPER3 expression and the number of CRLM. Our data demo...
Source: Tumor Biology - Category: Cancer & Oncology Source Type: research