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Article

Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

1
Kidney Research Center, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
2
Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
3
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 33303, Taiwan
4
Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital, Hsinchu Branch, Hsin-chu 31064, Taiwan
5
Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsin-chu 30015, Taiwan
6
Graduate Institute of Natural Products, Chang Gung University, Tao-Yuan 33303, Taiwan
7
Department of Pathology and Laboratory Medicine, Taoyuan Armed Forces General Hospital, Tao-Yuan 32551, Taiwan
8
Biomedical Engineering Department, Ming Chuan University, Tao-Yuan 33348, Taiwan
9
Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Tao-Yuan 33303, Taiwan
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Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
12
Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Received: 22 October 2019 / Revised: 17 December 2019 / Accepted: 18 December 2019 / Published: 21 December 2019
(This article belongs to the Special Issue Biomolecules and Cancer Prevention)
Daphne genkwa, a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid’s cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor ‘forkhead box protein M1’ (FOXM1) and downstream FOXM1-regulated proteins related to epithelial–mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent. View Full-Text
Keywords: liver cancer; hydroxygenkwanin; epithelial–mesenchymal transition; FOXM1; miR-320a liver cancer; hydroxygenkwanin; epithelial–mesenchymal transition; FOXM1; miR-320a
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MDPI and ACS Style

Chou, L.-F.; Chen, C.-Y.; Yang, W.-H.; Chen, C.-C.; Chang, J.-L.; Leu, Y.-L.; Liou, M.-J.; Wang, T.-H. Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression. Biomolecules 2020, 10, 20. https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010020

AMA Style

Chou L-F, Chen C-Y, Yang W-H, Chen C-C, Chang J-L, Leu Y-L, Liou M-J, Wang T-H. Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression. Biomolecules. 2020; 10(1):20. https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010020

Chicago/Turabian Style

Chou, Li-Fang, Chi-Yuan Chen, Wan-Hua Yang, Chin-Chuan Chen, Junn-Liang Chang, Yann-Lii Leu, Miaw-Jene Liou, and Tong-Hong Wang. 2020. "Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression" Biomolecules 10, no. 1: 20. https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010020

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