title: Integrating microRNA and mRNA expression profiles in response to radiation-induced injury in rat lung.
abstract: OBJECTIVE
  Exposure to radiation provokes cellular responses, which are likely regulated by gene expression networks. MicroRNAs are small non-coding RNAs, which regulate gene expression by promoting mRNA degradation or inhibiting protein translation. The expression patterns of both mRNA and miRNA during the radiation-induced lung injury (RILI) remain less characterized and the role of miRNAs in the regulation of this process has not been studied. The present study sought to evaluate miRNA and mRNA expression profiles in the rat lung after irradiation.
  
  
  METHODS
  Male Wistar rats were subjected to single dose irradiation with 20 Gy using 6 MV x-rays to the right lung. (A dose rate of 5 Gy/min was applied). Rats were sacrificed at 3, 12 and 26 weeks after irradiation, and morphological changes in the lung were examined by haematoxylin and eosin. The miRNA and mRNA expression profiles were evaluated by microarrays and followed by quantitative RT-PCR analysis.
  
  
  RESULTS
  A cDNA microarray analysis found 2183 transcripts being up-regulated and 2917 transcripts down-regulated (P ≤ 0.05, ≥2.0 fold change) in the lung tissues after irradiation. Likewise, a miRNAs microarray analysis indicated 15 miRNA species being up-regulated and 8 down-regulated (P ≤ 0.05). Subsequent bioinformatics analyses of the differentially expressed mRNA and miRNAs revealed that alterations in mRNA expression following irradiation were negatively correlated with miRNAs expression.
  
  
  CONCLUSIONS
  Our results provide evidence indicating that irradiation induces alterations of mRNA and miRNA expression in rat lung and that there is a negative correlation of mRNA and miRNA expression levels after irradiation. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of radiation-induced lung injury. In summary, RILI does not develop gradually in a linear process. In fact, different cell types interact via cytokines in a very complex network. Furthermore, this study suggests that microRNAs may serve an important role in the pathogenesis of RILI and that understanding their role in RILI may have a significant effect on patient management and diagnosis in the future.
authors.forename: Ling
authors.initials: L
authors.lastname: Xie
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Rensheng
authors.initials: R
authors.lastname: Lai
authors.forename: Weiqun
authors.initials: W
authors.lastname: Ding
authors.forename: ChuanJun
authors.initials: C
authors.lastname: Song
authors.forename: XingJun
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Radio-oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215001, China. wjinchang@sina.com.
authors.forename: Jinchang
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D005720:Gamma Rays / Q000009:adverse effects*; D020869:Gene Expression Profiling; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics*; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger