| Literature DB >> 27846390 |
Hui-Lung Sun1, Ri Cui2, JianKang Zhou3, Kun-Yu Teng4, Yung-Hsuan Hsiao5, Kotaro Nakanishi6, Matteo Fassan7, Zhenghua Luo2, Guqin Shi8, Esmerina Tili9, Huban Kutay4, Francesca Lovat2, Caterina Vicentini10, Han-Li Huang11, Shih-Wei Wang12, Taewan Kim13, Nicola Zanesi2, Young-Jun Jeon2, Tae Jin Lee2, Jih-Hwa Guh14, Mien-Chie Hung15, Kalpana Ghoshal4, Che-Ming Teng16, Yong Peng17, Carlo M Croce18.
Abstract
MicroRNAs (miRNA) are mostly downregulated in cancer. However, the mechanism underlying this phenomenon and the precise consequence in tumorigenesis remain obscure. Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. In liver cancer, the ERK-mediated XPO5 suppression reduces miR-122, increases microtubule dynamics, and results in tumor development and drug resistance. Analysis of clinical specimens further showed that XPO5 phosphorylation is associated with poor prognosis for liver cancer patients. Our study reveals a function of ERK in miRNA biogenesis and suggests that modulation of miRNA export has potential clinical implications.Entities:
Keywords: ERK; Exportin-5; Pin1; drug resistance; global downregulation; liver cancer; miR-122; miRNA; microtubule; nuclear export
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Year: 2016 PMID： 27846390 PMCID： PMC5127275 DOI： 10.1016/j.ccell.2016.10.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743