miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth

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-b...

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Main Authors:	Mihailovich, Marija, Bremang, Michael, Spadotto, Valeria, Musiani, Daniele, Vitale, Elena, Varano, Gabriele, Zambelli, Federico, Mancuso, Francesco M., Cairns, David A., Pavesi, Giulio, Casola, Stefano, Bonaldi, Tiziana
Format:	Online
Language:	English
Published:	Nature Pub. Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667639/

id	pubmed-4667639
recordtype	oai_dc
spelling	pubmed-46676392015-12-10 miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth Mihailovich, Marija Bremang, Michael Spadotto, Valeria Musiani, Daniele Vitale, Elena Varano, Gabriele Zambelli, Federico Mancuso, Francesco M. Cairns, David A. Pavesi, Giulio Casola, Stefano Bonaldi, Tiziana Article 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. Nature Pub. Group 2015-11-10 /pmc/articles/PMC4667639/ /pubmed/26555894 http://dx.doi.org/10.1038/ncomms9725 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mihailovich, Marija Bremang, Michael Spadotto, Valeria Musiani, Daniele Vitale, Elena Varano, Gabriele Zambelli, Federico Mancuso, Francesco M. Cairns, David A. Pavesi, Giulio Casola, Stefano Bonaldi, Tiziana
spellingShingle	Mihailovich, Marija Bremang, Michael Spadotto, Valeria Musiani, Daniele Vitale, Elena Varano, Gabriele Zambelli, Federico Mancuso, Francesco M. Cairns, David A. Pavesi, Giulio Casola, Stefano Bonaldi, Tiziana miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
author_facet	Mihailovich, Marija Bremang, Michael Spadotto, Valeria Musiani, Daniele Vitale, Elena Varano, Gabriele Zambelli, Federico Mancuso, Francesco M. Cairns, David A. Pavesi, Giulio Casola, Stefano Bonaldi, Tiziana
author_sort	Mihailovich, Marija
title	miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
title_short	miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
title_full	miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
title_fullStr	miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
title_full_unstemmed	miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth
title_sort	mir-17-92 fine-tunes myc expression and function to ensure optimal b cell lymphoma growth
description	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.
publisher	Nature Pub. Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667639/
_version_	1613508873496297472

miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth

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