Melatonin suppresses hepatocellular carcinoma progression via lncRNA-CPS1-IT-mediated HIF-1α inactivation

Tong Hong Wang, Chi Hao Wu, Chau Ting Yeh, Shih Chi Su, Shih Min Hsia, Kung Hao Liang, Chin Chuan Chen, Chuen Hsueh*, Chi Yuan Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


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 in vivo 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.

Original languageEnglish
Pages (from-to)82280-82293
Number of pages14
Issue number47
Publication statusPublished - 2017


  • Epithelial-mesenchymal transition
  • HIF-1α
  • Hepatocellular carcinoma
  • LncRNA-CPS1-IT1
  • melatonin

ASJC Scopus subject areas

  • Oncology


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