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Distinctive microRNA expression signatures in proton-irradiated mice

Authors
  • Khan, Shahid Yar1
  • Tariq, Muhammad Akram1, 2
  • Perrott, James Patrick1
  • Brumbaugh, Christopher Drew1
  • Kim, Hyunsung John1
  • Shabbir, Muhammad Imran1, 3
  • Ramesh, Govindarajan T.4
  • Pourmand, Nader1
  • 1 University of California Santa Cruz, Department of Biomolecular Engineering, Santa Cruz, CA, 95064, USA , Santa Cruz (United States)
  • 2 Texas Southern University, Center for Bionanotechnology and Environmental Research, Houston, TX, 77004, USA , Houston (United States)
  • 3 International Islamic University, Department of Bioinformatics and Biotechnology, Faculty of Basic Applied Sciences, Sector H10, Islamabad, Pakistan , Islamabad (Pakistan)
  • 4 Norfolk State University, Molecular Toxicology Laboratory, Center for Biotechnology and Biomedical Sciences, 700 Park Avenue, Norfolk, VA, 23504, USA , Norfolk (United States)
Type
Published Article
Journal
Molecular and Cellular Biochemistry
Publisher
Springer-Verlag
Publication Date
Jul 02, 2013
Volume
382
Issue
1-2
Pages
225–235
Identifiers
DOI: 10.1007/s11010-013-1738-z
Source
Springer Nature
Keywords
License
Yellow

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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