Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family
Name
JnBaptiste-Dicer loss and recovery induce.pdf
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1.36 MB
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Author(s)
JnBaptiste, Courtney Kenneil
Gurtan, Allan
Thai, Kevin K.
Lu, Victoria
Bhutkar, Arjun
Jacks, Tyler E.
Sharp, Phillip A.
Date Issued
April 2017
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Citation
JnBaptiste et al. “Dicer Loss and Recovery Induce an Oncogenic Switch Driven by Transcriptional Activation of the Oncofetal Imp1–3 Family.” Genes & Development 31, 7 (April 2017): 674–687 © 2017 JnBaptiste et al
Version
Final published version
Abstract
MicroRNAs(miRNAs) are post-transcriptional regulators of gene expressioncritical for organismal viability. Changes inmiRNAactivity arecommonin cancer, buthowthese changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated bymiRNAs. Wepresent analysis of the gene expression and phenotypic changes associated with globalmiRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genesImp1, Imp2, and Imp3(Imp1–3) that is up-regulated primarily transcriptionally > 100-fold uponDicer loss and is resistant to resilencing by complete restoration of miRNA activity. This Dicer-resistant epigenetic switch confers tumorigenicity to these cells. Let-7 targets Imp1–3 are required for this tumorigenicity and feed back to reinforce and sustain expression of the oncogenic network. Together, these Dicer-resistant genes constitute an mRNA expression signature that is present in numerous human cancers and is associated with poor survival.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1101/GAD.296301.117
