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Myricetin Suppresses the Propagation of Hepatocellular Carcinoma via Down-Regulating Expression of YAP

1
Institute of Integrated Medicine, Binzhou Medical University, Yantai 264003, China
2
School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, China
3
Key Laboratory of Tumour Molecular Biology, Department of Clinical Medicine, Binzhou Medical University, Yantai 264003, China
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(4), 358; https://doi.org/10.3390/cells8040358
Received: 12 March 2019 / Revised: 11 April 2019 / Accepted: 16 April 2019 / Published: 17 April 2019
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Abstract

Myricetin is a naturally occurring flavonoid with protective effects against a variety of cancers. However, the molecular mechanism of myricetin against hepatocellular carcinoma (HCC) has still not been fully elucidated. Previous studies have indicated that YAP is essential for cancer initiation and progression. However, whether YAP contributes to the anti-cancer effects of myricetin remains unclear. Herein, we aimed to investigate the effect of myricetin on HCC, and identify the underlying mechanisms. We report that myricetin induced apoptosis and proliferation inhibition in HepG2 and Huh-7 cells. Myricetin inhibited expression of YAP by promoting its phosphorylation and subsequent degradation. Myricetin inhibited YAP expression by stimulating kinase activation of LATS1/2. Knockdown expression of LATS1/2 by shRNA attenuated myricetin-induced phosphorylation and degradation of YAP. Furthermore, myricetin sensitized HCC cells to cisplatin treatment through inhibiting YAP and its target genes, both in vitro and in vivo. The identification of the LATS1/2-YAP pathway as a target of myricetin may help with the design of novel strategies for human HCC prevention and therapy. View Full-Text
Keywords: hepatocellular carcinoma; myricetin; LATS1/2-YAP; sensitization hepatocellular carcinoma; myricetin; LATS1/2-YAP; sensitization
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Li, M.; Chen, J.; Yu, X.; Xu, S.; Li, D.; Zheng, Q.; Yin, Y. Myricetin Suppresses the Propagation of Hepatocellular Carcinoma via Down-Regulating Expression of YAP. Cells 2019, 8, 358.

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