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

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机构： [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu (China)

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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 μm, 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. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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出版当年[2019]版：

大类 | 3 区化学

小类 | 3 区化学综合

最新[2023]版：

大类 | 3 区化学

小类 | 4 区化学：综合

第一作者：

第一作者机构： [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu (China)

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通讯机构： [*1]Chengdu Institute of Biology Chinese Academy of Sciences Chengdu (China)

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