[Micro-RNAs as biomarkers of radiation-induced injuries]. / Les micro-ARN comme biomarqueurs des lésions radio-induites.

In the event of a radiological or nuclear emergency following an accident or malicious act, potentially involving many victims, medical care requires the identification and diagnosis of individuals exposed to high doses of ionizing radiation as quickly as possible. While an initial screening can be carried out directly in the field, additional biological in-lab analyses are required to refine the diagnosis and optimize the therapeutic management of victims. The fast and simultaneous management of many patients is limited by currently established techniques. To overcome these constraints, the use of new biomarkers to predict the risk and severity of radiation-induced injuries is under investigation. This synthesis summarizes the latest scientific advances demonstrating the potential of microRNAs as biomarkers of radiationinduced injuries, highlighting their relevance for human health care and radioprotection.

Title: Les micro-ARN comme biomarqueurs des lésions radio-induites. Abstract: En cas d'urgence radiologique ou nucléaire résultant d'un accident ou d'un acte de malveillance, la prise en charge médicale requiert l'identification et le diagnostic des individus exposés à de fortes doses de rayonnements ionisants le plus rapidement possible. Bien qu'un triage préliminaire puisse être effectué directement sur le terrain, une analyse complémentaire en laboratoire est nécessaire pour affiner le diagnostic. Les techniques actuellement utilisées limitent la prise en charge rapide et simultanée de nombreux patients. Afin de pallier ces contraintes, l'utilisation de nouveaux biomarqueurs pour prédire le risque et la gravité des lésions radio-induites est à l'étude. Dans cette revue, nous abordons le potentiel des micro-ARN comme biomarqueurs pour le pronostic des lésions radio-induites et leur pertinence pour une utilisation en radioprotection chez l'homme.

microRNA blood signature for localized radiation injury.

A radiological accident, whether from industrial, medical, or malicious origin, may result in localized exposure to high doses of ionizing radiations, leading to the development of local radiation injury (LRI), that may evolve toward deep ulceration and necrosis of the skin and underlying tissues. Early diagnosis is therefore crucial to facilitate identification and management of LRI victims. Circulating microRNAs (miRNA) have been studied as potential diagnostic biomarkers of several diseases including hematological defects following whole-body irradiation (WBI). This study aims to identify a blood miRNA signature associated with LRI in a preclinical C57BL/6J mouse model of hindlimb irradiation using different 10-MV X-ray doses that lead to injuries of different severities. To this end, we first performed broad-spectrum plasma miRNA profiling, followed by a targeted validation step, on two independent animal cohorts. Using a multivariate sparse partial least square discriminant analysis, we identified a panel of eight circulating miRNAs able to segregate mice according to LRI severity. Interestingly, these miRNAs were previously associated with WBI (miR-150-5p, miR-342-3p, miR-146a-5p), inflammation (miR-18a-5p, miR-148b-3p, miR-532-5p) and skin diseases (miR-139-5p, miR-195-5p). Our results suggest the use of circulating miRNAs as suitable molecular biomarkers for LRI prognosis and diagnosis.