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Published on: April 18, 2025
Melatonin suppresses hepatocellular carcinoma progression via lncRNA-CPS1-IT-mediated HIF-1α inactivation
Tong-Hong Wang1,2,3, Chi-Hao Wu4, Chau-Ting Yeh3
1Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Abstract:
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.
Insights
Melatonin, a key hormone, shows promise in treating liver cancer (HCC). It inhibits cancer cell growth and spread by regulating specific gene pathways, offering a potential new therapy for hepatocellular carcinoma.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Melatonin, a pineal hormone, regulates circadian rhythms and exhibits antitumor properties.
- The precise mechanisms of melatonin's anticancer effects are not fully understood.
- Limited research exists on melatonin's role in hepatocellular carcinoma (HCC), a significant malignancy.
Purpose of the Study:
- To investigate the antitumor effects of melatonin in HCC.
- To elucidate the molecular mechanisms behind melatonin's action in HCC.
Main Methods:
- In vitro studies on HCC cell lines assessing proliferation, migration, and invasion.
- Analysis of gene expression, including transcription factor FOXA2 and lncRNA-CPS1-IT1.
- In vivo experiments to evaluate tumor growth suppression.
Main Results:
- Melatonin significantly inhibited HCC cell proliferation, migration, and invasion.
- Melatonin upregulated FOXA2 expression, leading to increased CPS1-IT1.
- CPS1-IT1 upregulation reduced HIF-1α activity, suppressing epithelial-mesenchymal transition (EMT) and metastasis.
- In vivo studies confirmed melatonin's tumor-suppressive effects.
Conclusions:
- Melatonin inhibits HCC progression through the FOXA2/CPS1-IT1 pathway, suppressing EMT.
- Melatonin demonstrates potential as a therapeutic agent for hepatocellular carcinoma.
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