Radiation-induced crosstalk between microRNAs and proteins of the endothelium: <em>In silico</em> analysis.

Ionising radiation causes damage at various levels in the exposed cell. The initial injury and the resulting cellular response to the damage involve complex crosstalk between the regulators of the DNA damage response recognition signalling and repair pathways. System-level research is required to gain more insight into these pathways. In this study we have used an in silico method to connect the altered proteome and miRNAome networks after radiation exposure by using Ingenuity Pathway Analysis tool and further verification for seed sequence matches by manually searching in microrna.org, mirDB, mirwalk, miRBase, and Targetscan databases. The endothelial cell was used as a model system as the endothelium is one of the main cellular systems damaged by ionising radiation. The interaction analysis revealed that changes at the miRNA level occur shortly after irradiation (4 and 12 hours) and thus often precede the alterations in the proteome that mostly take place later (24 hours). The two networks are closely intertwined emphasizing the regulatory role of miRNAs in the protein expression. Beside the well described pathways of the initial radiation response, such as oxidative stress and mitochondrial dysfunction, additional pathways such as Rho signalling (Rho family GTPases, Rho GDI and RhoA signalling) are involved in the endothelial response. In conclusion, the in silico analysis presented here is a valuable tool for identification of radiation targets and biomarkers for further validation. Furthermore, it can be used for any cellular or tissue model of interest