Identification of specific gene expression after exposure to low dose ionizing radiation revealed through integrative analysis of cDNA microarray data and the interactome

Accumulating reports suggest that the biological effects of low- and high- dose ionizing radiation (LDIR and HDIR) are qualitatively different and might cause different effects in human skin. To better understand the potential risks of LDIR, we analyzed three cDNA microarray datasets from the Gene Expression Omnibus database. A pathway analysis showed that genes in immune-associated pathways were upregulated while those in cancer-associated pathways were downregulated in skin exposed to LDIR as compared with non-irradiated control skin. Consistently, according to a comparative gene ontology analysis, “antigen presentation and processing” was the most different gene ontology between the LIDR and HDIR transcriptomes. To identify key molecules regulated by LDIR, we constructed a protein-protein interaction network analysis using topological metrics. One of the key molecules with a high network scores was E1A binding protein p300 (EP300), which is a potential target of a new therapeutic strategy to promote anti-tumor immunity. Our results showed that LDIR exposure mainly induced the upregulation of immune-related genes including chemokines (CXCL1, CXCL2, and CXCL5) and interleukins (IL1B, IL11, IL6, IL15, and IL7). Additionally, LDIR induced the upregulation of antigen processing and presentation-related genes including CIITA, HLA-DQB1, and KIF26A, but these genes were downregulated in HDIR-exposed skin. Our protein network interaction results indicated that EP300 is downregulated by the immune response in skin after LDIR exposure.