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

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.
Authors	Marija Mihailovich, Michael Bremang, Valeria Spadotto, Daniele Musiani, Elena Vitale, Gabriele Varano, Federico Zambelli, Francesco M Mancuso, David A Cairns, Giulio Pavesi, Stefano Casola, Tiziana Bonaldi
Journal	Nature communications (Nat Commun) Vol. 6 Pg. 8725 (Nov 10 2015) ISSN: 2041-1723 [Electronic] England
PMID	26555894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	ELAV-Like Protein 1 Elavl1 protein, mouse MIRN17-92 microRNA, mouse MicroRNAs Mirn17 microRNA, mouse Mirn20 microRNA, mouse Myc protein, mouse Proteome Proto-Oncogene Proteins c-myc Checkpoint Kinase 2 Chek2 protein, mouse
Topics	Animals Cell Line, Tumor Checkpoint Kinase 2 (genetics, metabolism) Cloning, Molecular ELAV-Like Protein 1 (genetics, metabolism) Gene Expression Regulation, Neoplastic (physiology) Lymphoma, B-Cell (metabolism) Mice Mice, Transgenic MicroRNAs (genetics, metabolism) Proteome Proto-Oncogene Proteins c-myc (genetics, metabolism)

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