Mihailovich, M, Bremang, M, Spadotto, V et al. (9 more authors) (2015) MiR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth. Nature Communications, 6. 8725. ISSN 2041-1723
Abstract
The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3′ untranslated region (UTR) analysis upon miR-17-19b overexpression. We identify over one hundred miR-17-19b targets, of which 40% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3' UTR shortening at different stages of tumorigenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2015 Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds) |
Funding Information: | Funder Grant number MRC G0802416 |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Dec 2015 14:31 |
Last Modified: | 04 Dec 2015 14:31 |
Published Version: | http://dx.doi.org/10.1038/ncomms9725 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/ncomms9725 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:92493 |