Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis

doi:10.1002/asia.201801461

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 国家天然药物工程技术研究中心 > 天然产物研究

	Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis
	Zheng, Yuanyuan 2; Pu, Wenchen 2; Li, Jiao 2; Shen, Xianyan 1; Zhou, Qiang 1; Fan, Xin 2; Yang, Sheng-Yong 2; Yu, Yamei 2; Chen, Qiang 2; Wang, Chun 1
刊名	CHEMISTRY-AN ASIAN JOURNAL
	2019
卷号	14 期号:1 页码:130-134
关键词	cancer flavonol hepatocellular carcinoma microRNA Pin1 XPO5
ISSN号	1861-4728
DOI	10.1002/asia.201801461
产权排序	2
文献子类	Article
英文摘要	Peptidyl-prolyl cis-trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7-(benzyloxy)-3,5-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one (AF-39) was identified as a novel Pin1 inhibitor. Biochemical tests indicate that AF-39 potently inhibits Pin1 activity with an IC50 values of 1.008 mu m, and also displays high selectivity for Pin1 among peptidyl prolyl isomerases. Furthermore, AF-39 significantly suppresses cell proliferation of HCC cells in a dose- and time-dependent manner. Mechanistically, AF-39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides a promising lead compound for HCC treatment, highlighting the therapeutic potential of miRNA-based therapy against human cancer.
学科主题	Chemistry
URL标识	查看原文
WOS关键词	PROLYL ISOMERASE PIN1 ; CANCER ; OVEREXPRESSION ; TUMORIGENESIS
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000454953700012
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30513]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Chinese Acad Sci, Chengdu Inst Biol, Chengdu, Sichuan, Peoples R China 2.Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr,and Collaborat Innovat Ctr Biotherapy, Chengdu, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Zheng, Yuanyuan,Pu, Wenchen,Li, Jiao,et al. Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis[J]. CHEMISTRY-AN ASIAN JOURNAL,2019,14(1):130-134.
APA	Zheng, Yuanyuan.,Pu, Wenchen.,Li, Jiao.,Shen, Xianyan.,Zhou, Qiang.,...&Peng, Yong.(2019).Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis.CHEMISTRY-AN ASIAN JOURNAL,14(1),130-134.
MLA	Zheng, Yuanyuan,et al."Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis".CHEMISTRY-AN ASIAN JOURNAL 14.1(2019):130-134.