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.