Ablation of Dicer leads to widespread perturbation of signaling pathways Journal Article


Authors: Sahasrabuddhe, N. A.; Huang, T. C.; Kumar, P.; Yang, Y.; Ghosh, B.; Leach, S. D.; Chaerkady, R.; Pandey, A.
Article Title: Ablation of Dicer leads to widespread perturbation of signaling pathways
Abstract: Dicer is an essential ribonuclease involved in the biogenesis of miRNAs. Previous studies have reported downregulation of Dicer in multiple cancers including hepatocellular carcinoma. To identify signaling pathways that are altered upon Dicer depletion, we carried out quantitative phosphotyrosine profiling of liver tissue from Dicer knockout mice. We employed antibody-based enrichment of phosphotyrosine containing peptides coupled with SILAC spike-in approach for quantitation. High resolution mass spectrometry-based analysis identified 349 phosphotyrosine peptides corresponding to 306 unique phosphosites of which 75 were hyperphosphorylated and 78 were hypophosphorylated. Several receptor tyrosine kinases including MET, PDGF receptor alpha, Insulin-like growth factor 1 and Insulin receptor as well as non-receptor tyrosine kinases such as Src family kinases were found to be hyperphosphorylated upon depletion of Dicer. In addition, signaling molecules such as IRS-2 and STAT3 were hyperphosphorylated. Activation of these signaling pathways has been implicated previously in various types of cancers. Interestingly, we observed hypophosphorylation of molecules including focal adhesion kinase and paxillin. Our study profiles the perturbed signaling pathways in response to dysregulated miRNAs resulting from depletion of Dicer. Our findings warrant further studies to investigate oncogenic effects of downregulation of Dicer in cancers. © 2015 Elsevier Inc. All rights reserved.
Keywords: signal transduction; controlled study; nonhuman; mass spectrometry; animal cell; mouse; animal tissue; mus; platelet derived growth factor alpha receptor; stat3 protein; animal experiment; animal model; protein tyrosine kinase; autophosphorylation; receptor tyrosine kinase; immunoblotting; cell migration; down regulation; somatomedin c; focal adhesion kinase; dicer; depletion; scatter factor receptor; phosphotyrosine; pathways; insulin receptor; focal adhesion; insulin receptor substrate 2; paxillin; silac; priority journal; article; enzyme depletion
Journal Title: Biochemical and Biophysical Research Communications
Volume: 463
Issue: 3
ISSN: 0006-291X
Publisher: Elsevier Science, Inc.  
Date Published: 2015-07-31
Start Page: 389
End Page: 394
Language: English
DOI: 10.1016/j.bbrc.2015.05.077
PROVIDER: scopus
PUBMED: 26032504
PMCID: PMC4696065
DOI/URL:
Notes: Export Date: 2 July 2015 -- Source: Scopus
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  1. Steven Leach
    37 Leach