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Bioinformatics: from nucleotids to networks (N2N)
Abstract
Several genes encoding for proteins involved in proliferation, invasion, and apoptosis are known to be direct miR-34a targets. Here, we used proteomics to screen for targets of miR-34a in neuroblastoma (NBL), a childhood cancer that originates from precursor cells of the sympathetic nervous system. We examined the effect of miR-34a overexpression using a tetracycline inducible system in two NBL cell lines (SHEP and SH-SY5Y) at early time points of expression (6, 12, and 24 h). Proteome analysis using post-metabolic labeling led to the identification of 2,082 proteins, and among these 186 were regulated (112 proteins down-regulated and 74 up-regulated). Prediction of miR-34a targets via bioinformatics showed that 32 transcripts held miR-34a seed sequences in their 3'-UTR. By combining the proteomics data with Kaplan Meier gene-expression studies, we identified seven new gene products (ALG13, TIMM13, TGM2, ABCF2, CTCF, Ki67, and LYAR) that were correlated with worse clinical outcomes. These were further validated in vitro by 3'-UTR seed sequence regulation. In addition, Michigan Molecular Interactions searches indicated that together these proteins affect signaling pathways that regulate cell cycle and proliferation, focal adhesions, and other cellular properties that overall enhance tumor progression (including signaling pathways such as TGF-beta, WNT, MAPK, and FAK). In conclusion, proteome analysis has here identified early targets of miR-34a with relevance to NBL tumorigenesis. Along with the results of previous studies, our data strongly suggest miR-34a as a useful tool for improving the chance of therapeutic success with NBL.
Keywords
PEDIATRIC-ONCOLOGY-GROUP, BREAST-CANCER CELLS, TGF-BETA, IDENTIFIES MIR-34A, TUMOR-SUPPRESSOR, STEM-CELLS, N-MYC, NUCLEOLAR PROTEIN, SELF-RENEWAL, FOCAL ADHESION

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Citation

Please use this url to cite or link to this publication:

Chicago
De Antonellis, Pasqualino, Marianeve Carotenuto, Jonathan Vandenbussche, Gennaro De Vita, Veronica Ferrucci, Chiara Medaglia, Iolanda Boffa, et al. 2014. “Early Targets of miR-34a in Neuroblastoma.” Molecular & Cellular Proteomics 13 (8): 2114–2131.
APA
De Antonellis, Pasqualino, Carotenuto, M., Vandenbussche, J., De Vita, G., Ferrucci, V., Medaglia, C., Boffa, I., et al. (2014). Early targets of miR-34a in neuroblastoma. MOLECULAR & CELLULAR PROTEOMICS, 13(8), 2114–2131.
Vancouver
1.
De Antonellis P, Carotenuto M, Vandenbussche J, De Vita G, Ferrucci V, Medaglia C, et al. Early targets of miR-34a in neuroblastoma. MOLECULAR & CELLULAR PROTEOMICS. 2014;13(8):2114–31.
MLA
De Antonellis, Pasqualino, Marianeve Carotenuto, Jonathan Vandenbussche, et al. “Early Targets of miR-34a in Neuroblastoma.” MOLECULAR & CELLULAR PROTEOMICS 13.8 (2014): 2114–2131. Print.
@article{6844169,
  abstract     = {Several genes encoding for proteins involved in proliferation, invasion, and apoptosis are known to be direct miR-34a targets. Here, we used proteomics to screen for targets of miR-34a in neuroblastoma (NBL), a childhood cancer that originates from precursor cells of the sympathetic nervous system. We examined the effect of miR-34a overexpression using a tetracycline inducible system in two NBL cell lines (SHEP and SH-SY5Y) at early time points of expression (6, 12, and 24 h). Proteome analysis using post-metabolic labeling led to the identification of 2,082 proteins, and among these 186 were regulated (112 proteins down-regulated and 74 up-regulated). Prediction of miR-34a targets via bioinformatics showed that 32 transcripts held miR-34a seed sequences in their 3'-UTR. By combining the proteomics data with Kaplan Meier gene-expression studies, we identified seven new gene products (ALG13, TIMM13, TGM2, ABCF2, CTCF, Ki67, and LYAR) that were correlated with worse clinical outcomes. These were further validated in vitro by 3'-UTR seed sequence regulation. In addition, Michigan Molecular Interactions searches indicated that together these proteins affect signaling pathways that regulate cell cycle and proliferation, focal adhesions, and other cellular properties that overall enhance tumor progression (including signaling pathways such as TGF-beta, WNT, MAPK, and FAK). In conclusion, proteome analysis has here identified early targets of miR-34a with relevance to NBL tumorigenesis. Along with the results of previous studies, our data strongly suggest miR-34a as a useful tool for improving the chance of therapeutic success with NBL.},
  author       = {De Antonellis, Pasqualino and Carotenuto, Marianeve and Vandenbussche, Jonathan and De Vita, Gennaro and Ferrucci, Veronica and Medaglia, Chiara and Boffa, Iolanda and Galiero, Alessandra and Di Somma, Sarah and Magliulo, Daniela and Aiese, Nadia and Alonzi, Alessandro and Spano, Daniela and Liguori, Lucia and Chiarolla, Cristina and Verrico, Antonio and Schulte, Johannes H and Mestdagh, Pieter and Vandesompele, Jo and Gevaert, Kris and Zollo, Massimo},
  issn         = {1535-9476},
  journal      = {MOLECULAR \& CELLULAR PROTEOMICS},
  keyword      = {PEDIATRIC-ONCOLOGY-GROUP,BREAST-CANCER CELLS,TGF-BETA,IDENTIFIES MIR-34A,TUMOR-SUPPRESSOR,STEM-CELLS,N-MYC,NUCLEOLAR PROTEIN,SELF-RENEWAL,FOCAL ADHESION},
  language     = {eng},
  number       = {8},
  pages        = {2114--2131},
  title        = {Early targets of miR-34a in neuroblastoma},
  url          = {http://dx.doi.org/10.1074/mcp.M113.035808},
  volume       = {13},
  year         = {2014},
}

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