Dataset Information

MiR-17-92 sustains lymphoma growth by fine-tuning MYC

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’ UTR analysis upon miR-17-19b overexpression. We identify over one hundred novel miR-17-19b targets, of which 40% are co-regulated by c-MYC. Down-regulation of a new miR-17/20 target 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): B Cell, Cell Culture

DISEASE(S): Lymphoma

SUBMITTER: Michael Bremang

LAB HEAD: Tiziana Bonaldi

PROVIDER: PXD002810 | Pride | 2015-11-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	F090401_ev_Bcell_HL1to1_C01.RAW	Raw
	F090401_ev_Bcell_HL1to1_C02.RAW	Raw
	F090401_ev_Bcell_HL1to1_C03.RAW	Raw
	F090401_ev_Bcell_HL1to1_C04.RAW	Raw
	F090401_ev_Bcell_HL1to1_C05.RAW	Raw

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Publications

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

Mihailovich Marija M Bremang Michael M Spadotto Valeria V Musiani Daniele D Musiani Daniele D Vitale Elena E Varano Gabriele G Zambelli Federico F Mancuso Francesco M FM Cairns David A DA Pavesi Giulio G Casola Stefano S Bonaldi Tiziana T

Nature communications 20151110

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 b ...[more]

PMID: 26555894

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