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Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis
Hailong Zhang1; Yanli Wang1; Jinzhuo Dou1; Yanmin Guo1; Jianfeng He1; Lian Li1; Xiaojia Liu1; Ran Chen1; Rong Deng1; Jian Huang1; Ruiyu Xie4; Xian Zhao1; Jianxiu Y1,2,3
2018
Source PublicationOncogene
ISSN0950-9232
Abstract

Argonaute2 (AGO2) is an effector of small RNA mediated gene silencing. Increasing evidence show that post-translational modifications of AGO2 can change miRNA activity at specific or global levels. Among the six mature miRNAs that are encoded by miR-17-92, miR-19b1 is the most powerful to exert the oncogenic properties of the entire cluster. Here we identify that AGO2 can be acetylated by P300/CBP and deacetylated by HDAC7, and that acetylation occurs at three sites K720, K493, and K355. Mutation of K493R/K720R, but not K355R at AGO2, inhibits miR-19b biogenesis. We demonstrate that acetylation of AGO2 specifically increases its recruiting pre-miR-19b1 to form the miPDC (miRNA precursor deposit complex), thereby to enhance miR-19b maturation. The motif UGUGUG in the terminal-loop of pre-miR19b1, as a specific processing feature that is recognized and bound by acetylated AGO2, is essential for the assembly of miRISC (miRNA-induced silencing complex) loading complex. Analyses on public clinical data, xenograft mouse models, and IHC and ISH staining of lung cancer tissues, further confirm that the high levels of both AGO2 acetylation and miR-19b correlate with poor prognosis in lung cancer patients. Our finding reveals a novel function of AGO2 acetylation in increasing oncogenic miR-19b biogenesis and suggests that modulation of AGO2 acetylation has potential clinical implications.

KeywordAcetylation Non-coding Rnas
DOIhttps://doi.org/10.1038/s41388-018-0530-7
Language英语
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Faculty of Health Sciences
Affiliation1.Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2.State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3.Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
4.Faculty of Health of Sciences, University of Macau, Macau 999078, China
Recommended Citation
GB/T 7714
Hailong Zhang,Yanli Wang,Jinzhuo Dou,et al. Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis[J]. Oncogene,2018.
APA Hailong Zhang.,Yanli Wang.,Jinzhuo Dou.,Yanmin Guo.,Jianfeng He.,...&Jianxiu Y.(2018).Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis.Oncogene.
MLA Hailong Zhang,et al."Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis".Oncogene (2018).
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