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Distinctive microRNA expression signatures in proton-irradiated mice

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Abstract

Proton particles comprise the most abundant ionizing radiation (IR) in outer space. These high energy particles are known to cause frequent double- and single-stranded DNA lesions that can lead to cancer and tumor formation. Understanding the mechanism of cellular response to proton-derived IR is vital for determining health risks to astronauts during space missions. Our understanding of the consequences of these high energy charged particles on microRNA (miRNA) regulation is still in infancy. miRNAs are non-coding, single-stranded RNAs of ~22 nucleotides that constitute a novel class of gene regulators. They regulate diverse biological processes, and each miRNA can control hundreds of gene targets. To investigate the effect of proton radiation on these master regulators, we examined the miRNA expression in selected mice organs that had been exposed to whole-body proton irradiation (2 Gy), and compared this to control mice (0 Gy exposure). RNA was isolated from three tissues (testis, brain, and liver) from treated and control mice and subjected to high-throughput small RNA sequencing. Bioinformatics analysis of small RNA sequencing data revealed dysregulation of (p < 0.05; 20 up- and 10 down-regulated) 14 mouse testis, 8 liver, and 8 brain miRNAs. The statistically significant and unique miRNA expression pattern found among three different proton-treated mouse tissues indicates a tissue-specific response to proton radiation. In addition to known miRNAs, sequencing revealed differential expression of 11 miRNAs in proton-irradiated mice that have not been previously reported in association with radiation exposure and cancer. The dysregulation of miRNAs on exposure to proton radiation suggest a possible mechanism of proton particles involvement in the onset of cell tumorgenesis. In summary, we have established that specific miRNAs are vulnerable to proton radiation, that such differential expression profile may depend upon the tissue, and that there are more miRNAs affected by proton radiation than have been previously observed.

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Acknowledgments

This study was supported in part by grants from the National Aeronautics and Space Administration Cooperative Agreements NCC9-165 and NNX08BA47A, National Institutes of Health [P01-HG000205], the National Science Foundation [DBI 0830141].

Author information

Author notes

  1. Muhammad Imran Shabbir

    Present address: Department of Bioinformatics and Biotechnology, Faculty of Basic Applied Sciences, International Islamic University, Sector H10, Islamabad, Pakistan

Authors and Affiliations

  1. Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, 95064, USA

    Shahid Yar Khan, Muhammad Akram Tariq, James Patrick Perrott, Christopher Drew Brumbaugh, Hyunsung John Kim, Muhammad Imran Shabbir & Nader Pourmand

  2. Center for Bionanotechnology and Environmental Research, Texas Southern University, Houston, TX, 77004, USA

    Muhammad Akram Tariq

  3. Molecular Toxicology Laboratory, Center for Biotechnology and Biomedical Sciences, Norfolk State University, 700 Park Avenue, Norfolk, VA, 23504, USA

    Govindarajan T. Ramesh

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  1. Shahid Yar Khan
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  2. Muhammad Akram Tariq
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  3. James Patrick Perrott
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  4. Christopher Drew Brumbaugh
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  5. Hyunsung John Kim
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  6. Muhammad Imran Shabbir
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  7. Govindarajan T. Ramesh
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  8. Nader Pourmand
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Correspondence to Nader Pourmand.

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Khan, S.Y., Tariq, M.A., Perrott, J.P. et al. Distinctive microRNA expression signatures in proton-irradiated mice. Mol Cell Biochem 382, 225–235 (2013). https://doi.org/10.1007/s11010-013-1738-z

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  • DOI: https://doi.org/10.1007/s11010-013-1738-z

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