Integrating MicroRNA And MRNA Expression Profiles In Response To Radiation-induced Injury In Rat Lung

Purpose: Exposure to radiation provokes cellular responses which are likelyregulated by gene expression networks. MicroRNAs are small non-coding RNAswhich regulate gene expression by promoting mRNA degradation or inhibitingprotein translation. The expression patterns of both mRNAs sand miRNAs during theradiation-induced lung injury (RILI) remain less characterized and the role ofmiRNAs in the regulation of this process has not been studied. The present studysought to evaluate miRNAs and mRNA expression profiles in the rat lung afterirradiation.Methods and Materials: Male Wistar rats were subjected to single dose irradiationwith20Gy to the right lung. Rats were sacrificed at3,12and26weeks afterirradiation, and morphological changes in the lung were examined by haematoxylinand eosin. The miRNAs and mRNA expression profiles were evaluated bymicroarrays and followed by quantitative RT-PCR analysis.Results: A cDNA microarray analysis found2183transcripts being up-regulated and2917transcripts down-regulated (P≤0.05,≥2.0-fold change) in the lung tissues afterirradiation. Likewise, a miRNAs microarray analysis indicated15miRNA speciebeing up-regulated and8down-regulated (P≤0.05). Subsequent bioinformaticsanalyses of the differentially expressed mRNAs and miRNAs revealed that alterationsin mRNA expression following irradiation were negatively correlated with miRNAsexpression. Conclusions: Our results provide evidence indicating that irradiation inducesalterations of mRNA and miRNA expression in rat lung and that there is a negativecorrelation of mRNA and miRNA expression levels after irradiation. These findingssignificantly advance our understanding of the regulatory mechanisms underlying thepathophysiology of irradiation-induced lung injury. Furthermore, this study suggeststhat miRNAs may serve as biodosimetrics markers of radiation exposure.