Yu Jia-Zi, Sun Ning, Bei Yi-Bing, Li Xiao-Bo, Lu Chao, Hua Lu-Chun
Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Mol Med Rep. 2017 Sep 25;16(6):7923-30. doi: 10.3892/mmr.2017.7596.
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.
大量研究表明，昼夜节律紊乱是可能促成人类结直肠癌（CRC）发生和发展的因素之一。最近，已证实microRNA-124可抑制CRC的肿瘤生长或转移。然而，在CRC调控中，microRNA-124（miR-124）与昼夜节律之间的相互作用机制尚不清楚。本研究表明，在高级别人类CRC组织以及侵袭性更强的结肠癌细胞系SW620和LOVO中，人类昼夜运动输出周期蛋白昼夜节律蛋白（hCLOCK）的蛋白表达水平显著升高，而miR-124减弱。进一步证明hCLOCK是miR-124的直接靶点。miR-124的上调显著抑制了LOVO细胞中hCLOCK的表达，从而抑制了其对LOVO细胞增殖和迁移的促进作用。总之，这些数据表明，hCLOCK在人类CRC中起增强作用，而mir-124起抑制作用。hCLOCK作为miR-124的直接靶点，其表达减弱导致CRC中hCLOCK表达增加和昼夜节律紊乱。
