Circadian gene hCLOCK contributes to progression of colorectal carcinoma and is directly regulated by tumor-suppressive microRNA-124

摘要

An abundance of studies has demonstrated that disruption of circadian rhythms is one of the factors that may contribute to the initiation and development of human colorectal carcinomas (CRCs). Recently, microRNA-124 has been demonstrated to suppress tumor growth or metastasis of CRCs. However, the mechanisms of cross-talk between microRNA-124 (miR-124) and circadian rhythms in the regulation of CRCs are poorly understood. The present study demonstrated that the protein expression levels of human circadian locomoter output cycles protein kaput (hCLOCK) is significantly increased, while miR-124 is attenuated in high-grade human CRC tissues and in the more invasive colorectal cancer cell lines SW620 and LOVO. It was further demonstrated that hCLOCK is a direct target of miR-124. Upregulation of miR-124 significantly inhibited hCLOCK expression in LOVO cells, and consequently inhibited its promoting effects on the proliferation and migration of LOVO cells. In conclusion, these data revealed that hCLOCK serves an enhancing role, whereas mir-124 serves a suppressive role, in human CRC. Attenuation of miR-124, of which hCLOCK is a direct target, leads to increased hCLOCK expression and disruption of circadian rhythms in CRC.