Wang Tong-Hong, Wu Chi-Hao, Yeh Chau-Ting, Su Shih-Chi, Hsia Shih-Min, Liang Kung-Hao, Chen Chin-Chuan, Hsueh Chuen, Chen Chi-Yuan
Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Graduate Institute of Health Industry Technology and Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan.
Oncotarget. 2017 Jul 18;8(47):82280-82293. doi: 10.18632/oncotarget.19316. eCollection 2017 Oct 10.
Melatonin is the primary pineal hormone that relays light/dark cycle information to the circadian system. It was recently reported to exert intrinsic antitumor activity in various cancers. However, the regulatory mechanisms underlying the antitumor activity of melatonin are poorly understood. Moreover, a limited number of studies have addressed the role of melatonin in hepatocellular carcinoma (HCC), a major life-threatening malignancy in both sexes in Taiwan. In this study, we investigated the antitumor effects of melatonin in HCC and explored the regulatory mechanisms underlying these effects. We observed that melatonin significantly inhibited the proliferation, migration, and invasion of HCC cells and significantly induced the expression of the transcription factor FOXA2 in HCC cells. This increase in FOXA2 expression resulted in upregulation of lncRNA-CPS1 intronic transcript 1 (CPS1-IT1), which reduced HIF-1α activity and consequently resulted in the suppression of epithelial-mesenchymal transition (EMT) progression and HCC metastasis. Furthermore, the results of the experiments confirmed that melatonin exerts tumor suppressive effects by reducing tumor growth. In conclusion, our findings suggested that melatonin inhibited HCC progression by reducing lncRNA-CPS1-IT1-mediated EMT suppression and indicated that melatonin could be a promising treatment for HCC.
褪黑素是主要的松果体激素，它将明暗周期信息传递给昼夜节律系统。最近有报道称，褪黑素在多种癌症中具有内在的抗肿瘤活性。然而，褪黑素抗肿瘤活性的调控机制尚不清楚。此外，仅有少数研究探讨了褪黑素在肝细胞癌（HCC）中的作用，HCC是台湾地区男女主要的致命性恶性肿瘤。在本研究中，我们研究了褪黑素对HCC的抗肿瘤作用，并探讨了其作用的调控机制。我们观察到，褪黑素显著抑制HCC细胞的增殖、迁移和侵袭，并显著诱导HCC细胞中转录因子FOXA2的表达。FOXA2表达的增加导致长链非编码RNA-CPS1内含子转录本1（CPS1-IT1）上调，从而降低HIF-1α活性，进而抑制上皮-间质转化（EMT）进程和HCC转移。此外，实验结果证实褪黑素通过减少肿瘤生长发挥肿瘤抑制作用。总之，我们的研究结果表明，褪黑素通过减少lncRNA-CPS1-IT1介导的EMT抑制来抑制HCC进展，并表明褪黑素可能是一种有前景的HCC治疗方法。
